In considerazione del particolare stato di emergenza dovuta all’epidemia da SARS-CoV-2 e della velocità con cui si stanno registrando ricerche sulle strategie per contrastare la Covid-19, il DEP ritiene importante monitorare e sintetizzare le informazioni relative alle prove di efficacia e sicurezza che si renderanno a mano a mano disponibili.

 

Stiamo per questo lavorando ad una revisione sistematica sull'efficacia dei farmaci per il trattamento della malattia COVID-19 che si aggiornerà costantemente nel tempo con la pubblicazione dei risultati di nuovi studi clinici.

FARMACI E COVID-19: COSA SAPPIAMO


IL NOSTRO LAVORO È IN PROGRESS


 

 

Trattamenti a confronto


clicca qui per andare alla versione in inglese delle tabelle di evidenza GRADE

Network degli interventi farmacologici per COVID-19


Sono inclusi solo gli studi con un numero di partecipanti superiore a 100

Aggiornamento al 28/06/2021

I NOSTRI METODI


Per l’identificazione, la valutazione e la sintesi dei risultati seguiremo un processo rigoroso e trasparente.


 

 

 

Identificazione di un nuovo trattamento

 

Criteri di inclusione

  • Popolazione: persone affette da COVID-19, come definito dagli autori dello studio. Nessun limite in base al genere o provenienza geografica
  • Intervento: Verranno considerati studi che valutano interventi farmacologici per il trattamento di persone con COVID-19, (es. antibiotici, anticorpi, antimalarici, antivirali, antiretrovirali, immunosoppressori/modulatori, inibitori della chinasi proteica) e la loro combinazione
  • Confronto: qualsiasi trattamento attivo, placebo o terapia standard
  • Esiti primari: mortalità per tutte le cause
  • Esiti secondari: negatività al test molecolare con metodo Real Time PCR per 2019-nCoV, PaO2/FiO2, durata della ventilazione meccanica, durata della degenza ospedaliera, miglioramento dell’imaging radiologico, eventi avversi, eventi avversi gravi
  • Disegno di studio: studi randomizzati controllati. Dal 1 marzo 2021 verranno considerati solo studi che hanno arruolato un numero di persone ≥100

Ricerca di trial

 

Ricerca bibliografica

Banche dati elettroniche:

  • Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library
  • MEDLINE (via OVID)
  • Embase (via OVID)
  • MedRxiv Health Sciences e bioRxiv Biology (articoli in pre-print)

La ricerca nelle banche dati predere l’utilizzo di specifiche strategie di ricerca che includono una combinazione di parole chiave, prese da un vocabolario medico controllato, e parole libere.

  • Registri di studi clinici: Clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP), Cochrane COVID-19 Register

Strategia di ricerca degli studi (adatta per MEDLINE-via OVID)

1

exp coronavirus/

2

((corona* or corono*) adj1 (virus* or viral* or virinae*)).ti,ab,kw.

3

(coronavirus* or coronovirus* or coronavirinae* or Coronavirus* or Coronovirus* or Wuhan* or Hubei* or Huanan or "2019-nCoV" or 2019nCoV or nCoV2019 or "nCoV-2019" or "COVID-19" or COVID19 or "CORVID-19" or CORVID19 or "WN-CoV" or WNCoV or "HCoV-19" or HCoV19 or CoV or "2019 novel*" or Ncov or "n-cov" or "SARS-CoV-2" or "SARSCoV-2" or "SARSCoV2" or "SARS-CoV2" or SARSCov19 or "SARS-Cov19" or "SARSCov-19" or "SARS-Cov-19" or Ncovor or Ncorona* or Ncorono* or NcovWuhan* or NcovHubei* or NcovChina* or NcovChinese*).ti,ab,kw.

4

(((respiratory* adj2 (symptom* or disease* or illness* or condition*)) or "seafood market*" or "food market*") adj10 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw.

5

((outbreak* or wildlife* or pandemic* or epidemic*) adj1 (China* or Chinese* or Huanan*)).ti,ab,kw.

6

"severe acute respiratory syndrome*".ti,ab,kw.

7

or/1-6

Selezione ed estrazione dei dati

 

Verranno selezionati gli studi ed estratti indipendentemente da due autori i seguenti dati:

  • Autore dello studio, anno di pubblicazione, disegno dello studio
  • Diagnosi, dimensione del campione, età media, genere, gravita della malattia, setting
  • Numero di pazienti assegnati a ciascun gruppo di trattamento, nome del farmaco, dosaggio, durata dell’intervento e periodo di follow up
  • Esiti primari e secondari

Valutazione della qualità globale degli studi

 

Per ogni singolo esito viene valutata la qualità (certezza) delle prove, considerando vari fattori quali:

  1. i possibili rischi di distorsione (bias) degli studi che contribuiscono a fornire informazioni su quell’esito;
  2. la variabilità (inconsistency) nelle stime di efficacia degli studi inclusi;
  3. la non diretta trasferibilità (indirectness) dei risultati al contesto di interesse;
  4. l’imprecisione quando gli studi includono pochi pazienti e/o si verificano pochi eventi;
  5. pubblicazione selettiva degli esiti, si tratta di una distorsione che si verifica quando la probabilità che un studio scientifico venga pubblicato dipende dal tipo di risultato.

 

La certezza delle prove viene sintetizzata in 4 livelli: alta, moderata, bassa, molto bassa.

Alto: Alto grado di certezza nei risultati. E’ molto improbabile che ulteriori studi possano cambiare la fiducia nella stima di effetto.

Moderato: Discreto grado di certezza nei risultati. È probabile che ulteriori studi possano confermare o cambiare la fiducia nella stima dell’effetto.

Basso: I risultati sono poco credibili. È necessaria ulteriore ricerca per ottenere stime affidabili sugli effetti positivi e negativi dell’intervento.

Molto basso: I dati esaminati sono inaffidabili. Non è possibile fare affidamento sulle stime di effetto disponibili.

Analisi statistica

 

In una prima fase verranno condotte, se possibile, meta-analisi pairwise per il confronto diretto tra due interventi. Nella meta-analisi:

  • Ogni studio è sintetizzato in una misura di effetto
  • Queste sintesi sono combinate in una stima di effetto globale che tiene in considerazione la quantità di informazioni disponibili per singolo studio
  • La misura di effetto complessivo consiste nell’effetto medio pesato dei risultati dei singoli studi
  • Si verifica se le variazioni dei risultati tra i vari studi sono più grandi di quelle attendibili in base al caso (eterogeneità)
  • I risultati della meta-analisi saranno presentati come dimensioni di effetto relativo usando il Rischio relativo (RR) o la Differenza tra medie standardizzata (SMD - a seconda che il dato sia dicotomico o continuo), con i relativi intervalli di confidenza al 95%, per ogni possibile coppia di trattamenti.

Network meta-analisi

  • La network meta-analisi (NMA), o meta-analisi a rete, è un metodo per sintetizzare le informazioni provenienti da una rete di studi scientifici che affrontano la stessa domanda ma che prevedono interventi diversi. Mentre una meta-analisi pairwise compara solo due confronti diretti, la NMA dispone a rete gli studi randomizzati, ed utilizza tutte le informazioni della rete, sia dirette che indirette, e può aumentare la precisione delle stime di effetto.
  • Nel nostro studio eseguiremo la NMA utilizzando un random effect model all'interno di un approccio «frequentista», assumendo un'uguale eterogeneità in tutti i confronti, e terremo conto delle correlazioni indotte da studi con più bracci. Il modello ci permetterà di stilare una classifica di quale sia il farmaco migliore per il trattamento del Covid-19. Eseguiremo la NMA in Stata 16 utilizzando il comando 'mvmeta' e le routine di Stata disponibili su www.mtm.uoi.gr. I risultati della meta-analisi e della NMA saranno applicati quando ragionevoli e presentati come dimensioni di effetto relativo sommario usando la odds ratio o la standardised mean difference (a seconda che il dato sia dicotomico o continuo), con i relativi intervalli di confidenza al 95%, per ogni possibile coppia di trattamenti.

Sintesi dei risultati

 

I dati verranno presentati in tabelle sinottiche in cui per ciascun esito vengono riassunti i risultati disponibili e viene valutata l’attendibilità/certezza delle prove presentate (alta, moderata, bassa, molto bassa).

Studi randomizzati inclusi


  1. Abbaspour Kasgari H, Moradi S, Shabani AM, Babamahmoodi F, Davoudi Badabi AR, Davoudi L, et al. Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial. J Antimicrob Chemother. 2020 Nov 1;75(11):3373-3378. doi: 10.1093/jac/dkaa332
  2. Abd-Elsalam S, Esmail ES, Khalaf M, Abdo EF, Medhat MA, Abd El Ghafar MS, et al. Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study. The American Journal of Tropical Medicine and Hygiene. 2020;103(4):1635-9.
  3. Abd-Elsalam S, Soliman S, Esmail ES, Khalaf M, Mostafa EF, Medhat MA, et al. Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine? a Randomized, Multicenter Trial. Biol Trace Elem Res. 2020 Nov 27. doi: 10.1007/s12011-020-02512-1 Epub ahead of print
  4. Abd-Elsalam S, Noor RA, Badawi R, Khalaf M, Esmail ES, Soliman S, et al. Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study. J Med Virol. 2021 Jun 2. doi: 10.1002/jmv.27122. Epub ahead of print
  5. ACTIV-3/TICO LY-CoV555 Study Group, Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, et al. A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. N Engl J Med. 2020 Dec 22:NEJMoa2033130. doi: 10.1056/NEJMoa2033130. Epub ahead of print
  6. Ader F, Peiffer-Smadja N, Poissy J, Bouscambert-Duchamp M, Belhadi D, Diallo A, et al. Antiviral drugs in hospitalized patients with COVID-19 - the DisCoVeRy trial. medRxiv. 2021:2021.01.08.20248149
  7. Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P; PLACID Trial Collaborators. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020 Oct 22;371:m3939. doi: 10.1136/bmj.m3939 Erratum in: BMJ. 2020 Nov 3;371:m4232.
  8. Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, et al. A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis. 2020 Dec 2:S1201-9712(20)32506-6. doi: 10.1016/j.ijid.2020.11.191 Epub ahead of print
  9. Alavi Darazam I, Pourhoseingholi MA, Shokouhi S, Naghibi Irvani SS, Mokhtari M, Shabani M, et al. Role of Interferon Therapy in Severe COVID-19: The COVIFERON Randomized Controlled Trial 2020. https://www.researchsquare.com/article/rs-136499/v1doi.org/10.21203/rs.3.rs-136499/v1
  10. AlQahtani M, Abdulrahman A, AlMadani A, AlAli SY, Al Zamrooni AM, Hejab A, et al. Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease. medRxiv. 2020:2020.11.02.20224303.
  11. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1317-1329. doi: 10.1001/jama.2020.17022
  12. Ansarin K, Tolouian R, Ardalan M, Taghizadieh A, Varshochi M, Teimouri S, et al. Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial. Bioimpacts. 2020;10(4):209-215. doi: 10.34172/bi.2020.27 Epub 2020 Jul 19
  13. Avendano-Sola C, Ramos-Martinez A,Munez-Rubio E,et al.. Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial. medRxiv 2020.08.26.20182444; 2020
  14. Babalola O, Bode C, Ajayi A, Alakaloko F, Akase I, Otrofanowei E, et al. Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double blind dose response study in Lagos. medRxiv. 2021:2021.01.05.21249131
  15. Bajpai M, Kumar S, Maheshwari A, Chhabra K, kale P, Gupta A, et al. Efficacy of Convalescent Plasma Therapy compared to Fresh Frozen Plasma in Severely ill COVID-19 Patients: A Pilot Randomized Controlled Trial. medRxiv. 2020:2020.10.25.20219337
  16. Balykova LA, Granovskaya MV, Zaslavskaya KY, Simakina EN, Agaf'ina AS, Ivanova AY, et al. New possibilities for targeted antiviral therapy for COVID-19. Results of a multi center clinical study of the efficacy and safety of using the drug Areplivir. Infectious diseases: News, Opinions, Training. 2020;9:16-29
  17. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764 Epub 2020 Oct 8
  18. Bikdeli B, Talasaz AH, Rashidi F, Bakhshandeh H, Rafiee F, Matin S. Intermediate vs Standard-dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to ICU: Ninety-day Results from the INSPIRATION Trial. Thromb Haemost. 2021 Apr 17. doi: 10.1055/a-1485-2372. Epub ahead of print.
  19. Blum VF, Cimerman S, Hunter JR, Tierno P, Lacerda A, Soeiro A, et al. Nitazoxanide In Vitro Efficacy Against SARS CoV-2 and In Vivo Superiority to Placebo to Treat Moderate COVID-19 – A Phase 2 Randomized Double-Blind Clinical Trial. 2021. Available at SSRN: https://ssrn.com/abstract=3763773
  20. Brown SM, Peltan ID, Webb B, Kumar N, Starr N, Grissom C, et al. Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial. Ann Am Thorac Soc. 2020 Aug;17(8):1008-1015. doi: 10.1513/AnnalsATS.202004-309SD PMID: 32425051; PMCID: PMC7393787
  21. Cadegiani FA, McCoy J, Wambier CG, Kovacevic M, Shapiro J, Sinclair R, et al. Proxalutamide (GT0918) Reduces the Rate of Hospitalization and Death in COVID-19 Male Patients: A Randomized Double-Blinded Placebo-Controlled Trial. Research Square; 2020. DOI: 10.21203/rs.3.rs-135303/v1.
  22. Cadegiani FA (b), McCoy J, Gustavo Wambier C, Vaño-Galván S, Shapiro J, Tosti A, et al. Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial. Cureus. 2021 Feb 22;13(2):e13492. doi: 10.7759/cureus.13492
  23. Cadegiani F A (a), Mccoy J, Gustavo Wambier C, Goren A. Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial (EAT-DUTA AndroCoV Trial – Biochemical). 2021. Cureus 13(2): e13047. doi: 10.7759/cureus.13047
  24. Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-1799. doi: 10.1056/NEJMoa2001282
  25. Cao Y, Wei J, Zou L, Jiang T, Wang G, Chen L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020 Jul;146(1):137-146.e3. doi: 10.1016/j.jaci.2020.05.019 Epub 2020 May 26
  26. Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, et al; Coalition Covid-19 Brazil I Investigators. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. N Engl J Med. 2020 Jul 23:NEJMoa2019014. doi: 10.1056/NEJMoa2019014 Epub ahead of print
  27. Chaccour C, Aina Casellasa A, Blanco-Di Matteo A, Pineda I, Fernandez-Montero A, Ruiz-Castillo P et al. The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial, EClinicalMedicine (2021), doi: 10.1016/j.eclinm.2020.100720
  28. Chen C, Zhang Y, Huang J, Yin P, Cheng Z, Wu J, et al. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. medRxiv. 2020:2020.03.17.20037432.
  29. Chen C-P, Lin Y-C, Chen T-C, Tseng T-Y, Wong H-L, Kuo C-Y, et al. A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19). medRxiv. 2020:2020.07.08.20148841
  30. Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, et al. [A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 May 25;49(2):215-219. Chinese. doi: 10.3785/j.issn.1008-9292.2020.03.03
  31. Chen J, Xia L, Liu L, Xu Q, Ling Y, Huang D, et al. Antiviral Activity and Safety of Darunavir/Cobicistat for the Treatment of COVID-19. Open Forum Infect Dis. 2020 Jun 21;7(7):ofaa241. doi: 10.1093/ofid/ofaa241
  32. Chen L, Zhang Z-y, Fu J-g, Feng Z-p, Zhang S-Z, Han Q-Y, et al. Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study. medRxiv. 2020:2020.06.19.20136093.
  33. Chen Z, Hu J, Zhang Z, Jiang S, Han S, Yan D, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv. 2020:2020.03.22.20040758.
  34. Cheng LL, Guan WJ, Duan CY, Zhang NF, Lei CL, Hu Y, et al. Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial. JAMA Intern Med. 2020 Sep 10:e205503. doi: 10.1001/jamainternmed.2020.5503 Epub ahead of print
  35. Chowdhury ATM, Shahbaz M, Karim MR, Islam J, Dan G, He S. A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients. EJMO 2021;5(1):63–70
  36. Choudhury IM, Shabnam N, Ahsan T, Kabir S, Khan R, Ahsan A. Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient. Bioresearch Communications-(BRC). 2021;7(1):919-23. http://www.bioresearchcommunications.com/index.php/brc/article/view/176
  37. CORIMUNO-19, Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial.. Lancet Respir Med.; 2021
  38. Corral L, Bahamonde A, Arnaiz delas Revillas F, Gomez-Barquero J, Abadia-Otero J, Garcia-Ibarbia C, et al. GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia. medRxiv. 2020:2020.06.17.20133579
  39. Dabbous, H.M., Abd-Elsalam, S., El-Sayed, M.H. et al. Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study. Arch Virol 166, 949–954 (2021). doi: 10.1007/s00705-021-04956-9
  40. Dabbous HM, El-Sayed MH,El Assal G,et al.. . A Randomized Controlled Study Of Favipiravir Vs Hydroxychloroquine In COVID-19 Management: What Have We Learned So Far?, 29 September 2020, PREPRINT (Version 1) available at Research Square doi: 10.21203/rs.3.rs-83677/v1+
  41. Davoudi-Monfared E, Rahmani H Khalili H al. et. Efficacy and safety of interferon beta-1a in treatment of severe COVID-19: A randomized clinical trial. medRxiv. doi: 10.1101/2020.05.28.20116467
  42. Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, et al; GRECCO-19 investigators. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized with Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136
  43. Dequin PF, Heming N, Meziani F, Plantefève G, Voiriot G, Badié Jet al; CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1298-1306. doi: 10.1001/jama.2020.16761
  44. DISCOVERY Trial:
    1. a. b. Ader F, Peiffer-Smadja N, Poissy J, Bouscambert-Duchamp M, Belhadi D, Diallo A, et al; DisCoVeRy study group. An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clin Microbiol Infect. 2021 May 25:S1198-743X(21)00259-7. doi: 10.1016/j.cmi.2021.05.020. Epub ahead of print
    2. b. c. Ader F, Bouscambert-Duchamp M, Hites M, Peiffer-Smadja N, Poissy J, Belhadi D, et al. Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial. SSRN Electronic Journal. 2021
  45. Duarte M, Pelorosso FG, Nicolosi L, Salgado MV, Vetulli H, Aquieri A, et al. Telmisartan for treatment of Covid-19 patients: an open randomized clinical trial. Preliminary report. medRxiv. 2020:2020.08.04.20167205.
  46. Dubée V, Roy P-M, Vielle B, Parot-Schinkel E, Blanchet O, Darsonval A, et al. A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19. medRxiv. 2020:2020.10.19.20214940.
  47. Edalatifard M, Akhtari M, Salehi M, Naderi Z, Jamshidi A, Mostafaei S, et al. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J. 2020 Sep 17:2002808. doi: 10.1183/13993003.02808-2020 Epub ahead of print
  48. Elgohary MA-S, Hasan EM, Ibrahim AA, Ahmed Abdelsalam MF, Abdel-Rahman RZ, Zaki AI, et al. Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: Randomized controlled trial. medRxiv. 2021:2021.05.19.21257429
  49. Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, Alcalá Díaz JF, López Miranda J, Bouillon R, Quesada Gomez JM. "Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study". J Steroid Biochem Mol Biol. 2020 Oct;203:105751. doi: 10.1016/j.jsbmb.2020.105751 Epub 2020 Aug 29
  50. Esquivel-Moynelo I, Perez-Escribano J, Duncan-Robert Y, Vazquez-Blonquist D, Bequet-Romero M et al. Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. medRxiv preprint doi: 10.1101/2020.07.29.20164251
  51. Feld JJ, Kandel C, Biondi MJ, Kozak RA, Zahoor MA, Lemieux C, et al. Peginterferon-lambda for the treatment of COVID-19 in outpatients. medRxiv. 2020:2020.11.09.20228098
  52. Fragoso-Saavedra S, Núñez I, Audelo-Cruz MB, Arias-Martínez S, Manzur-Sandoval D, Quintero-Villegas A, et al. Pyridostigmine in adults with severe SARS-CoV-2 infection: the PISCO trial. medRxiv 2021.04.28.21255834; doi: 10.1101/2021.04.28.21255834
  53. Furtado RHM, Berwanger O, Fonseca HA, Corrêa TD, Ferraz LR, Lapa M, et al; COALITION COVID-19 Brazil II Investigators. Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. Lancet. 2020 Oct 3;396(10256):959-967. doi: 10.1016/S0140-6736(20)31862-6 Epub 2020 Sep 5
  54. Galan LEB, Santos NMD, Asato MS, Araújo JV, de Lima Moreira A, Marques Araújo AM, et al. Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection. Pathog Glob Health. 2021 Mar 8:1-8. doi: 10.1080/20477724.2021.1890887. Epub ahead of print
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  136. Sivapalan P, Suppli Ulrik C, Sophie Lapperre T, Dahlin Bojesen R, Eklöf J, Browatzki A, Torgny Wilcke J, et al; ProPAC-COVID study group. Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19-a randomised double-blinded placebo-controlled trial. Eur Respir J. 2021 Jun 3:2100752. doi: 10.1183/13993003.00752-2021. Epub ahead of print
  137. Sivapalasingam S, Lederer DJ, Bhore R, Hajizadeh N, Criner G, Hossain R, et al. A Randomized Placebo-Controlled Trial of Sarilumab in Hospitalized Patients with Covid-19. medRxiv. DOI: 10.1101/2021.05.13.21256973
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  141. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al; BACC Bay Tocilizumab Trial Investigators. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020 Oct 21:NEJMoa2028836. doi: 10.1056/NEJMoa2028836. Epub ahead of print.
  142. Tabarsi P, Barati S, Jamaati H, Haseli S, Marjani M, Moniri A, et al. Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial. Int Immunopharmacol. 2020 Nov 13:107205. doi: 10.1016/j.intimp.2020.107205 Epub ahead of print
  143. Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020 May 14;369:m1849. doi: 10.1136/bmj.m1849
  144. Tang X, Feng YM, Ni JX, Zhang JY, Liu LM, Hu K, et al. Early Use of Corticosteroid May Prolong SARS-CoV-2 Shedding in Non-Intensive Care Unit Patients with COVID-19 Pneumonia: A Multicenter, Single-Blind, Randomized Control Trial. Respiration. 2021 Jan 22:1-11. doi: 10.1159/000512063. Epub ahead of print.
  145. Tardif J-C, Bouabdallaoui N, L’Allier PL, Gaudet D, Shah B, Pillinger MH, et al. Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19. Medrxiv. 2021
  146. Temesgen Z, Burger CD, Baker J, Polk C, Libertin C, Kelley C, et al. Lenzilumab efficacy and safety in newly hospitalized covid-19 subjects: results from the live-air phase 3 randomized double-blind placebo-controlled trial. medRxiv [Preprint]. 2021 May 5:2021.05.01.21256470. doi: 10.1101/2021.05.01.21256470
  147. Tolouian R, Mulla ZD, Jamaati H, Babamahmoodi A, Marjani M, Eskandari R, et al. Effect of bromhexine in hospitalized patients with COVID-19. Journal of Investigative Medicine. 2021. Epub ahead of print: doi: 10.1136/jim-2020-001747
  148. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al; COALITION COVID-19 Brazil III Investigators. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1307-1316. doi: 10.1001/jama.2020.17021
  149. Tornling G, Batta R, Porter J, Bengtsson T, Parmar K, Kashiva R, et al. The angiotensin type 2 receptor agonist C21 restores respiratory function in COVID19 - a double-blind, randomized, placebo-controlled Phase 2 trial. medRxiv. 2021:2021.01.26.21250511
  150. Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, et al. Efficacy and Safety of Favipiravir, an Oral RNA-Dependent RNA Polymerase Inhibitor, in Mild-to-Moderate COVID-19: A Randomized, Comparative, Open-Label, Multicenter, Phase 3 Clinical Trial. Int J Infect Dis. 2020 Nov 16:S1201-9712(20)32453-X. doi: 10.1016/j.ijid.2020.11.142 Epub ahead of print
  151. Ulrich RJ, Troxel AB, Carmody E, Eapen J, Bäcker M, DeHovitz JA, et al. Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients, Open Forum Infectious Diseases, Volume 7, Issue 10, October 2020, ofaa446 doi: 10.1093/ofid/ofaa446
  152. Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, Zampieri FG, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ. 2021;372:n84.
  153. Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, et al. Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol. 2020 Dec;2(12):e764-e773. doi: 10.1016/S2665-9913(20)30341-6 Epub 2020 Sep 28
  154. Wang D, Fu B, Peng Z, Yang D, Han M, Li M, et al. Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial. Front Med. 2021 Mar 9:1–9. doi: 10.1007/s11684-020-0824-3. Epub ahead of print
  155. Wang M, Zhao Y, Hu W, Zhao D, Zhang Y, Wang T, et al Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -- a Single-Center, Randomized, Controlled Clinical Trial. Clin Infect Dis. 2020 Sep 21:ciaa1417. doi: 10.1093/cid/ciaa1417 Epub ahead of print
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Studi esclusi e motivo di esclusione


Studio Motivo di esclusione
Abdelalim 2021 Tipo di confronto ed esiti che non rientrano nei criteri di inclusione
Alavi-Moghaddam 2021 Numero di pazienti/partecipanti basso (<100)*
Ali 2021 Numero di pazienti/partecipanti basso (<100)*
Altay 2020 Tipo di esiti che non rientrano nei criteri di inclusione
Amat Santos 2020 Tipo di popolazione che non rientra nei criteri di inclusione: pazienti con stenosi aortica a rischio COVID-19
Amaravadi 2021 Numero di pazienti/partecipanti basso (<100)*
Arefin 2021 Tipo di confronto che non rientra nei criteri di inclusione e dati non utlizzabili
Backer 2021 Tipo doi popolazione che non rientra nei criteri di inclusione
Balcells 2020 Tipo di confronto che non rientra nei criteri di inclusione: stesso trattamento in tempi diversi
Balykova 2020b Articolo in cirillico
Balykova 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Barnabas 2020 Tipo di popolazione che non rientra nei criteri di inclusione: contatto con una persona con una recente infezione nota di SARS-CoV-2.
Lenin Beltran Gonzalez Tipo di esiti che non rientrano nei criteri di inclusione
Bian 2021 Tipo di popolazione che non rientra nei criteri di inclusione: volontari non malati
Borba 2020 Tipo di confronto che non rientra nei criteri di inclusione: stesso farmaco a dosaggi diversi.
Cadegiani 2020a Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Cadegiani 2020b Tipo di esiti che non rientrano nei criteri di inclusione
Cadegiani 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Calzetta 2021 Tipo di disegno di studio che non rientra nei criteri di inclusione
Chalala 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Cohen 2021 Tipo di confronto che non rientra ne criteri di inclusione
Cremer 2021 Numero di pazienti/partecipanti basso (<100)*
Cruz 2020 Tipo di esiti che non rientrano nei criteri di inclusione.
Davoodi 2020 Tipo di popolazione che non rientra nei criteri di inclusione: COVID-19 sospetta e non confermata e tipo di esiti.
Delgado-Enciso 2020 Tipo di intervento che non rientra nei criteri di inclusione
de Alencar 2020 Tipo di popolazione che non rientra nei criteri di inclusione: parte dei partecipanti con COVID-19 sospetta e non confermata
de Ligt 2021 Numero di pazienti/partecipanti basso (<100)*
Doi 2020 Tipo di confronto che non rientra nei criteri di inclusione: stesso trattamento in tempi diversi
Duarte Silveira 2021 Tipo di intervento che non rientra nei criteri di inclusione
Elgazzar 2021 Tipo di popolazione che non rientra nei criteri di inclusione: studio di profilassi con popolazione mista contatti e contagiati
Faisal 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Faqihi 2021 Numero di pazienti/partecipanti basso (<100)*
Faqihi 2021 Numero di pazienti/partecipanti basso (<100)*
Farahani 2020 Tipo di esiti che non rientrano nei criteri di inclusione
Freedenberg 2021 Tipo di esiti e intervento che non rientrano nei criteri di inclusione
Fu 2020 Tipo di esiti che non rientrano nei criteri di inclusione
Gaborit 2021 Numero di pazienti/partecipanti basso (<100)*
Gagliardini 2021 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Geriak 2021 Numero di pazienti/partecipanti basso (<100)*
Ghaderkhani 2020 Tipo di esiti che non rientrano nei criteri di inclusione
Ghaderkhani 2021 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Goldman 2020 Tipo di confronto che non rientra nei criteri di inclusione: stesso farmaco somministrato per durate diverse
Gonzalez-Ochoa 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Guenezan 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Hamidi-Alamdari 2021 Numero di pazienti/partecipanti basso (<100)*
Holman 2021 Nessun dato utile
Hemila 2020 Tipo di popolazione che non rientra nei criteri di inclusione
Huang Y 2021 Tipo di intervento che non rientra nei criteri di inclusione
Husain 2020 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Ibrahim 2020 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Inspiration Investigators 2021 Tipo di confronto: due dosi dello stesso farmaco
Jordans 2021 Numero di pazienti/partecipanti basso (<100)* e dati non utilizzabili
Khoo 2021 Tipo di confronto che non rientra ne criteri di inclusione e numero di pazienti/partecipanti basso (<100)*
Lattman 2021 Numero di pazienti/partecipanti basso (<100)*
Lee 2021 Numero di pazienti/partecipanti basso (<100)*
Li G 2020 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Lopes 2021 Tipo di confronto che non rientra nei criteri di inclusione
Lyngbakken 2020 Tipo di esiti che non rientrano nei criteri di inclusione
Mammen 2021 Tipo di studio e obiettivo: ri-analisi trial incluso
Mareev 2021 Articolo in cirillico
MeiLan 2020 Nessun dato utilizzabile
Mennecier 2021 Tipo di obiettivo che non rientra nie criteri di inclusione
Mitjà 2020b Tipo di popolazione che non rientra nei criteri di inclusione: storia recente di esposizione a contatto ravvicinato a un paziente con Covid-19 con un caso confermato dalla PCR
Myasnikov 2021 Articolo in cirillico
Okumuş 2021 Numero di pazienti/partecipanti basso (<100)*
Onal 2021 Tipo di intervento che non rientra nei criteri di inclusione
Padmanabham 2020 Tipo di intervento che non rientra nei criteri di inclusione
Painter 2020 Tipo di popolazione ed esiti che non rientrano nei criteri di inclusione
Pandit 2021 Numero di pazienti/partecipanti basso (<100)*
Patel 2021 Numero di pazienti/partecipanti basso (<100)*
Podder 2020 Dati non utilizzabili
Pott-Junior 2021 Numero di pazienti/partecipanti basso (<100)*
Pouladzadeh 2021 Numero di pazienti/partecipanti basso (<100)*
PRINCIPLE Trial Collaborative Group 2021 Tipo di popolazione, tipo di esiti che non rientrano nei criteri di inclusione
Purwati 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Puskarich 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Raess 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Rashad 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Rashid 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Rastogi 2020 Tipo di popolazione: pazienti con deficit di vitamina D e tipo di intervento: non farmacologico vitamina D
Ravichandran 2021 Numero di pazienti/partecipanti basso (<100)*
Rea-Neto 2021 Tipo di intervento che non rientra nei criteri di inclusione
Rojas-Serrano 2021 Tipo di popolazione che non rientra nei criteri di inclusione
Roostaei 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Roozbeh 2020 Tipo di esiti che non rientrano nei criteri di inclusione
Rossignol 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Salehzadeh 2021 Tipo di esiti che non rientrano nei criteri di inclusione e dati non utilizzabili
Sali 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Samaha 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Samimagham 2021 Numero di pazienti/partecipanti basso (<100)*
Sayad 2021 Numero di pazienti/partecipanti basso (<100)*
Seet 2021 Tipo di popolazione che non rientra nei criteri di inclusione e tipo di obiettivo
Sehgal 2021 Numero di pazienti/partecipanti basso (<100)*
Shahbaznejad 2021 Numero di pazienti/partecipanti basso (<100)*
Shih 2020 Dati non utilizzabili, ri-analisi studio incluso (Wang 2020)
Shoumann 2021 Tipo di popolazione che non rientra nei criteri di inclusione: studio di profilassi con popolazione di contatti
Siahkali 2020 Tipo di intervento che non rientra nei criteri di inclusione
Sigamani 2020 Tipo di disegno di studio: studio di fattibilità di un RCT
Silva 2021 Numero di pazienti/partecipanti basso (<100)*
Singh 2021 Numero di pazienti/partecipanti basso (<100)*
Skipper 2020 Tipo di popolazione che non rientra nei criteri di inclusione: mista con sospetti COVID-19 non confermati e tipo di esiti
Stanevich 2021 Tipo di disegno di studio: studio di fattibilità di un RCT
Supady 2021 Numero di pazienti/partecipanti basso (<100)*
Talaschian 2021 Numero di pazienti/partecipanti basso (<100)*
Thakar 2021 Tipo di esiti che non rientrano nei criteri di inclusione
Veerapaneni Spoorthi 2021 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Wang 2020 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Weinreich 2021 Tipo di popolazione e tipo di esiti che non rientrano nei criteri di inclusione
Yadegarinia 2020 Tipo di disegno di studio che non rientra nei criteri di inclusione: studio non randomizzato
Zafar 2021 Abstract: dati non utilizzabili
Zarehoseinzade 2021 Numero di pazienti/partecipanti basso (<100)*
Zhao 2021 Numero di pazienti/partecipanti basso (<100)*
Zhong 2020 Tipo di intervento che non rientra nei criteri di inclusione: acido α-lipoico

* criterio inserito a partire dal 1 marzo 2021

 

 

Bibliografia studi esclusi

 

  1. Abdelalim AA, Mohamady AA, Elsayed RA, Elawady MA, Ghallab AF. Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: A randomized controlled trial. Am J Otolaryngol. 2021 Jan 4;42(2):102884. doi: 10.1016/j.amjoto.2020.102884. Epub ahead of print.
  2. Alavi-moghaddam M, Haghighi M, Sabaghian T, Soroureddin Z, Chaboki BG. Safety and Efficacy of Sofosbuvir in Hospitalized Adult Patients with SARS-CoV-2: A Preliminary Report. Available at SSRN: https://ssrn.com/abstract=3790463 or http://dx.doi.org/10.2139/ssrn.3790463
  3. Ali S, Uddin SM, Shalim E, Sayeed MA, Anjum F, Saleem F, et al. Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial. EClinicalMedicine. 2021 Jun 4:100926. doi: 10.1016/j.eclinm.2021.100926. Epub ahead of print
  4. Alltay O, Yang H, Aydin M, Alkurt G, Altunal LN, Kim W, et al. Combined metabolic cofactor supplementation accelerates recovery in mild-to-moderate COVID-19. medRxiv. 2020:2020.10.02.20202614.
  5. Amat-Santos IJ, Santos-Martinez S, López-Otero D, et al. Ramipril in High-Risk Patients With COVID-19. J Am Coll Cardiol. 2020;76(3):268-276. doi:10.1016/j.jacc.2020.05.040
  6. Amaravadi RK, Giles, Carberry LM, Hyman MC, Frank I, Nasta SD, et al. Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial medRxiv 2021.02.22.21252228; doi: https://doi.org/10.1101/2021.02.22.21252228
  7. Arefin MK, Rumi SKNF, Uddin AKMN, Banu SS, Khan M, Kaiser A, Chowdhury JA, Khan MAS, Hasan MJ. Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial. Indian J Otolaryngol Head Neck Surg. 2021 May 18:1-5. doi: 10.1007/s12070-021-02616-7. Epub ahead of print
  8. Balcells ME, Rojas L, Le Corre N, Martínez-Valdebenito C, Ceballos ME, Ferrés M, et al. Early Anti-SARS-CoV-2 Convalescent Plasma in Patients Admitted for COVID-19: A Randomized Phase II Clinical Trial. medRxiv. 2020:2020.09.17.20196212.
  9. Backer V, Sjöbring U, Sonne J, Weiss A, Hostrup M, Johansen HK, et al. A randomized, double-blind, placebo-controlled phase 1 trial of inhaled and intranasal niclosamide: A broad spectrum antiviral candidate for treatment of COVID-19. The Lancet Regional Health – Europe
  10. Balykova LA, Govorov AV, Vasilyev AO, Simakina EN, Agafyina AS, Ivanova AYu, et al. Characteristics of COVID-19 and possibilities of early causal therapy. Results of favipiravir use in clinical practice. Infekc. bolezni (Infectious diseases). 2020; 18(3): 30–40. (In Russian). doi: 10.20953/1729-9225-2020-3-30-40
  11. Balykova L, Pavelkina V, Shmyreva N, Pyataev N, Selezneva N, Shepeleva O, et al. EFFICACY AND SAFETY OF SOME ETIOTROPIC THERAPEUTIC SCHEMES FOR TREATING PATIENTS WITH NOVEL CORONAVIRUS INFECTION (COVID-19). Pharmacy & Pharmacology. 2020;8:150-9
  12. Barnabas RV, Brown ER, Bershteyn A, Stankiewicz Karita HC, Johnston C, Thorpe LE, et al. Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial. Ann Intern Med. 2020 Dec 8:M20-6519. doi: 10.7326/M20-6519. Epub ahead of print. PMID: 33284679; PMCID: PMC7732017.
  13. Beltran Gonzalez JL, González Gámez M, Mendoza Enciso EA, Esparza Maldonado RJ, Palacios DH, Dueñas Campos S, et al. Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial. medRxiv 2021.02.18.21252037; doi: https://doi.org/10.1101/2021.02.18.21252037
  14. Bian H, Zheng ZH, Wei D, Wen A, Zhang Z, Lian JQ, et al. Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial. Signal Transduct Target Ther. 2021 May 17;6(1):194. doi: 10.1038/s41392-021-00603-6. PMID: 34001849; PMCID: PMC8127508
  15. Borba MGS, Val FFA, Sampaio VS, et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(4):e208857. Published 2020 Apr 24. doi: https://doi.org/10.1001/jamanetworkopen.2020.8857
  16. Cadegiani FA, Goren A, Wambier CG, McCoy J. Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients. medRxiv 2020.10.31.20223883; doi: https://doi.org/10.1101/2020.10.31.20223883.
  17. Cadegiani FA, McCoy J, Wambier CG, et al. 5-Alpha-Reductase Inhibitors Reduce Remission Time of COVID-19: Results From a Randomized Double Blind Placebo Controlled Interventional Trial in 130 SARS-CoV-2 Positive Men. medRxiv 2020.11.16.20232512; doi: https://doi.org/10.1101/2020.11.16.20232512
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Dipartimento di Epidemiologia del Servizio Sanitario Regionale, Regione Lazio - Laura Amato l.amato@deplazio.it