Classificação de desfechos clínicos em 30 dias reportados por investigadores ou realizada por meio de um comitê de revisores independente em pacientes com síndrome coronariana aguda incluídos no estudo randomizado SECURE-PCI

Objective: Using data from the SECURE-PCI trial, which included patients with acute coronary syndrome randomized to two loading doses (before and 24 hours after a planned percutaneous coronary intervention) of atorvastatin or placebo, this study aims to: describe the organization and methodology of the clinical events classification process performed in this study; to compare the clinical outcome rates derived from two forms of outcome identification: 1-defined by the clinical events classification committee 2-outcomes reported directly by the site investigators and describe the treatment effect of the atorvastatin doses or placebo on outcomes validated by an independent clinical event classification committee or reported directly by investigators. Methods: This study evaluates the SECURE-PCI outcomes reported directly by the sites investigators in the study case report form. SECURE-PCI was a multicenter, national, pragmatic, double-blind, with intention-to-treat analysis, randomized controlled trial. The primary objective is to determine if administration of loading doses of atorvastatin reduced the rate of major cardiovascular events in 30 days in patients with acute coronary syndrome undergoing a planned percutaneous coronary intervention. The study investigator filled out the case reported forms with information regarding outcomes or possible outcomes and this information was validated by a clinical event classification committee. Results: The SECURE-PCI clinical event classification process includes the following steps: identifying suspected events, evaluating event-related source documents by at least two independent physician reviewers, and determining the final event classification. From 4191 patients included in the trial, the site investigators reported 249 patients with major cardiovascular events. 38 (15.26%) of these were not validated by the event classification committee; on the other hand, the investigators did not report major cardiovascular events in 68 (24.37%) patients, which were validated by the clinical event classification committee. The treatment effect of the SECURE-PCI study considering the rate of combined outcomes validated by the clinical event classification committee versus the combined outcome rate reported directly by the investigators results in Hazard ratio = 0.88, 95% CI (69, 1.11), p = 0.27 versus Hazard ratio = 1.03, 95% CI (0.80, 1.32), p = 0.82. Considering the group of patients who underwent percutaneous coronary intervention, the treatment effect of the combined outcome that was validated by the clinical events classification versus that reported by the investigators was Hazard ratio = 0.72, 95% CI (0.54; 0.96), p = 0.02) versus Hazard ratio = 0.85, 95% CI (0.63, 1.17), p = 0.32. Conclusions: Considering all the combined events reported by the investigators, 84.8% were confirmed by the clinical events classification committee however, the investigators did not report major cardiovascular events in 68 (24,37%) patients, which were identified by the clinical event classification committee. The outcomes with highest difference between those reported by the investigators and those validated by the clinical events classification were periprocedure myocardial infarction and non-planned revascularization. In general results from the SECURE-PCI were similar considering data classified by an independent clinical event classification committee or reported by investigators. However, in the pre-specified subgroup analysis of patients who underwent percutaneous coronary intervention, the results were different: when outcomes reported directly by the investigators were analyzed, we did not find significant differences between the patients who received loading doses of statin and the control group. On the other hand, when using clinical events classification results, we demonstrated that the use of loading doses of statin reduced major cardiovascular events in this subgroup of patients.Objetivo: Utilizando dados do ensaio clínico multicêntrico randomizado SECURE–PCI, que incluiu pacientes com síndrome coronariana aguda randomizados para 2 doses de ataque (uma dose antes e outra 24 horas após a intervenção coronária percutânea planejada) de atorvastatina ou placebo, este estudo tem por objetivos apresentar a organização e metodologia da classificação de eventos clínicos aplicadas; comparar as taxas de desfechos clínicos derivadas de 2 formas de identificação de desfechos: 1) definidos pelo comitê de classificação de eventos clínicos e 2) reportados diretamente pelos centros investigadores e descrever o efeito de tratamento das doses de ataque da atorvastatina comparadas com placebo em desfechos clínicos classificados por um comitê independente de revisores ou reportados diretamente por investigadores. Métodos: Este estudo avalia os desfechos apresentados pelos participantes do SECURE-PCI e reportados diretamente pelos investigadores na ficha de coleta de dados do estudo. O SECURE-PCI foi um ensaio clínico randomizado com alocação sigilosa, multicêntrico, nacional, pragmático, com avaliação cega dos desfechos e com análise por intenção de tratar com o objetivo primário de determinar se a administração de doses de ataque de atorvastatina reduz a taxa de eventos cardiovasculares maiores em 30 dias em pacientes com síndrome coronariana aguda com programação de intervenção coronária percutânea. Os investigadores do estudo preenchiam a ficha de coleta com informações sobre desfechos ou dados indicativos de possíveis desfechos que posteriormente eram validados por um comitê de classificação de eventos clínicos. Resultados: O processo de classificação de eventos clínicos do SECURE-PCI inclui as etapas de identificação de possíveis eventos suspeitos, avaliação dos documentos relacionados ao evento por pelo menos 2 revisores médicos especialistas independentes e a determinação da classificação do evento. De um total de 4.191 pacientes, os investigadores reportaram 249 pacientes com desfechos combinados. Destes, 38 (15,26%) não foram validados pelo comitê de classificação de eventos, por outro lado, os investigadores deixaram de reportar desfechos combinados em 68 (24,37%) pacientes, os quais foram validados pelo comitê de classificação de eventos por meio da identificação de gatilhos na ficha de coleta de dados dos pacientes. A comparação do efeito de tratamento do estudo SECURE-PCI considerando a taxa de desfechos combinados validados pelo comitê de classificação de eventos clínicos versus a taxa de desfechos combinados reportados diretamente pelos investigadores resulta em: Hazard ratio = 0,88, IC95% (0,69; 1,11), p=0,27 versus Hazard ratio = 1,03, IC95% (0,80; 1,32), p = 0,82. Considerando o grupo de pacientes que realizaram a intervenção coronária percutânea, o efeito de tratamento do desfecho combinado que foi validado pela classificação de eventos clínicos versus o reportado pelos investigadores apresentou-se assim: Hazard ratio = 0,72, IC95% (0,54; 0,96), p=0,02 versus Hazard ratio = 0,85, IC95% (0,63; 1,17), p = 0,32. Conclusões: Dentre todos os eventos combinados que foram reportados pelos investigadores, 84,8% foram confirmados pelos avaliadores independentes e o comitê de classificação de eventos identificou mais 68 desfechos combinados (24,37% do total). Os desfechos que apresentaram maior divergência entre os reportados pelos investigadores e os validados pela classificação de eventos clínicos foram infarto periprocedimento e revascularização de urgência. Os resultados gerais do estudo SECURE-PCI foram semelhantes nas análises dos eventos classificados por um comitê independente de revisores ou reportados pelos investigadores quando considerada a amostra total do estudo. Entretanto, na análise de subgrupo de pacientes submetidos a intervenção coronária percutânea, os resultados foram distintos. Os resultados advindos da análise dos desfechos reportados diretamente pelos investigadores não apresentam diferenças significativas entre os pacientes que receberam doses de ataque de estatina e o grupo controle. Já os resultados analisados após a classificação de eventos clínicos demonstraram que o uso da estatina reduziu eventos cardiovasculares maiores neste subgrupo de pacientes.Dados abertos - Sucupira - Teses e dissertações (2019

Plano de análise estatística para o Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). Ensaio controlado randomizado

RESUMO Fundamentação: O estudo Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) é um ensaio clínico internacional, multicêntrico, randomizado, pragmático e controlado com ocultação da alocação que envolve 120 unidades de terapia intensiva no Brasil, Argentina, Colômbia, Espanha, Itália, Polônia, Portugal, Malásia e Uruguai, com o objetivo primário de determinar se o recrutamento alveolar gradual máximo associado com titulação da pressão positiva expiratória final, ajustada segundo a complacência estática do sistema respiratório (estratégia ART), é capaz de aumentar, quando comparada aos resultados do tratamento convencional (estratégia ARDSNet), a sobrevivência em 28 dias de pacientes com síndrome do desconforto respiratório agudo. Objetivo: Descrever o processo de gerenciamento dos dados e o plano de análise estatística em um ensaio clínico internacional. Métodos: O plano de análise estatística foi delineado pelo comitê executivo e revisado pelo comitê diretivo do ART. Foi oferecida uma visão geral do delineamento do estudo, com foco especial na descrição de desfechos primário (sobrevivência aos 28 dias) e secundários. Foram descritos o processo de gerenciamento dos dados, o comitê de monitoramento de dados, a análise interina e o cálculo do tamanho da amostra. Também foram registrados o plano de análise estatística para os desfechos primário e secundários, e os subgrupos de análise pré-especificados. Detalhes para apresentação dos resultados, inclusive modelos de tabelas para as características basais, adesão ao protocolo e efeito nos desfechos clínicos, foram fornecidos. Conclusão: Em acordo com as melhores práticas em ensaios clínicos, submetemos nossos planos de análise estatística e de gerenciamento de dados para publicação antes do fechamento da base de dados e início das análises. Antecipamos que este documento deve prevenir viés em análises e incrementar a utilidade dos resultados a serem relatados. Registro do estudo: Número no registro ClinicalTrials.gov NCT01374022

Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome : a Randomized Clinical Trial

IMPORTANCE The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. OBJECTIVE To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. INTERVENTIONS An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. MAIN OUTCOMES AND MEASURES The primary outcomewas all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stayventilator-free days through day 28pneumothorax requiring drainage within 7 daysbarotrauma within 7 daysand ICU, in-hospital, and 6-month mortality. RESULTS A total of 1010 patients (37.5% femalemean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.2095% CI, 1.01 to 1.42P =.041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%HR, 1.1895% CI, 1.01 to 1.38P =.04), decreased the number of mean ventilator-free days (5.3 vs 6.4difference, -1.195% CI, -2.1 to -0.1P =.03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%difference, 2.0%95% CI, 0.0% to 4.0%P =.03), and the risk of barotrauma (5.6% vs 1.6%difference, 4.0%95% CI, 1.5% to 6.5%P =.001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. CONCLUSIONS AND RELEVANCE In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. (C) 2017 American Medical Association. All rights reserved.Brazilian Ministry of HealthBrazilian Ministry of HealthHCor Res Inst, Sao Paulo, BrazilUniv Sao Paulo, Cardiopulmonary Dept, Div Pulm, Heart Inst Incor, Sao Paulo, BrazilHosp Moinhos de Vento, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilFed Univ Sao Paulo UNIFESP, Anesthesiol Pain & Intens Care Dept, Sao Paulo, BrazilUniv Sao Paulo, Dept Epidemiol, Sch Publ Hlth, Sao Paulo, BrazilHosp Maternidade Sao Vicente Paulo, Barbalha, BrazilHosp Nereu Ramos, Florianopolis, SC, BrazilHosp Unimed Vitoria, Vitoria, BrazilHosp & Prontosocorro 28 Agosto, Manaus, Amazonas, BrazilUniv Sao Paulo, Unidade Emergencia Hosp Clin FMRP, Ribeirao Preto, BrazilHosp Estadual Dr Jayme Santos Neves, Serra, BrazilFundacao Univ Fed Grande Dourados, Univ Hosp, Dourados, BrazilUniv ICESI, Fdn Valle Lili, Dept Intens Care Med, Cali, ColombiaHosp Univ Oeste Parana, Cascavel, BrazilHosp Pablo Tobon Uribe, Medellin, ColombiaHosp Clin Porto Alegre, Porto Alegre, RS, BrazilHosp Reg Hans Dieter Schmidt, Joinville, BrazilUniv Malaya, Med Ctr, Kuala Lumpur, MalaysiaJagiellonian Univ, Med Coll, Dept Intens Care & Perioperat Med, Krakow, PolandHosp Nacl Alejandro Posadas, Moron, ArgentinaFed Univ Sao Paulo UNIFESP, Anesthesiol Pain & Intens Care Dept, Sao Paulo, BrazilWeb of Scienc

Rhinorrhea-free days up to day 10.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.</div

Vomit-free days up to day 10.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.</div

Cough-free days up to day 10.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.</div

Symptoms free-days up to day 10.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.</div

Mean SARS-CoV-2 viral load log 10 between groups.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.</div

Respiratory symptoms-free days up to day 10.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.</div