Covid-19 Living Data

Trial NCT04469114
Publication Guimaraes P, N Engl J Med, 2021 (published paper)
Dates: 2020-09-16 to 2020-12-13
Funding: Private (Pfizer)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Brazil Follow-up duration (days): 28
Inclusion criteria	Male or female participants older than 18 years; Laboratory-confirmed SARS-CoV-2 infection as determined by RT-PCR prior to day 1; Evidence of Covid-19 pneumonia assessed by radiographic imaging (chest x-ray or chest computed tomography scan); Hospitalization for less than 72 hours and receiving standard of care treatment for Covid-19
Exclusion criteria	Need for noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) on day 1; History of or known current thrombosis (only if current thrombosis was suspected by the investigator, imaging testing was recommended to exclude thrombosis before enrollment); Personal or first-degree family history of blood clotting disorders; Patients who were immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (e.g., azathioprine, cyclosporine); Any current malignancy or lymphoproliferative disorders that required active treatment; Severe hepatic impairment, defined as Child-Pugh class C; Severe anemia (hemoglobin <8 g/dL); An absolute lymphocyte count <500 cells/mm3; An absolute neutrophil count <1000 cells/mm3; Known allergy to tofacitinib; Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that might increase the risk associated with study participation or, in the investigator’s judgment, make the participant inappropriate for the study; Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of Covid-19) including but not limited to: active herpes zoster infection; known active tuberculosis or history of inadequately treated tuberculosis; known hepatitis B, hepatitis C, or human immunodeficiency virus; Patients who had received any of the following treatment regimens specified in the timeframes outlined below within 4 weeks prior to the first dose of study intervention: any Janus kinase (JAK) inhibitors, potent immunosuppressants, or any biologic agents including interleukin (IL)-6 inhibitors (e.g., tocilizumab) or IL-1 inhibitors (e.g., anakinra) within the past 30 days; any potent cytochrome P450 inducer, such as rifampin, within the past 28 days or 5 half-lives, whichever was longer; Patients who had received any of the following treatment regimens specified in the timeframes outlined below within 48 hours prior to the first dose of study intervention: estrogen-containing contraception or treatment with herbal supplements; Patients who had received treatment with glucocorticoids equivalent to prednisone or methylprednisolone >20 mg/day for equal or more than 14 consecutive days prior to screening; Patients who were current participants in other clinical trials
Interventions
	Treatment Tofacitinib 10 mg orally twice a day for up to 14 days or until hospital discharge, whichever was earlier
	Control Placebo
Participants
	Randomized 289 participants (n₁=144 / n₂= 145)
	Characteristics of participants N=289 Mean age : 56 188 males Severity : Mild: n=71 / Moderate: n=181/ Severe: n=37 Critical: n=0
Primary outcome
	In the register Death or respiratory failure until Day 28 [ Time Frame: 28 days ]
	In the report Death or respiratory failure during the 28 days of follow-up
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Low
General comment	In addition to the published article with supplementary appendices, the protocol with statistical analysis plan and prospective study registry were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There no substantive differences between the published article and the registry or protocol in population, procedures, outcomes or intervention and control treatments.