Covid-19 Living Data

Trial NCT04724629
Publication STRUCK - Bonifacio L, SSRN (2022) (preprint)
Dates: 2021-01-06 to 2021-07-09
Funding: Mixed (Rede Vírus (MCTI - Ministerio Da Ciencia, Tecnologia e Inovacoes) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) (National Council for Scientific and Technological Development). Company Clinigen provided bottles of Interleukin-2 (ProleukinTM) free of charge.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Brazil Follow-up duration (days): 45
Inclusion criteria	18 Years and older hospitalized moderate to severe presentation of Covid-19 positive result in the quantitative real-time PCR (qPCR) test for SARS-CoV-2 in the respiratory tract pneumonia confirmed by chest imaging and 1) Respiratory rate ≥ 24 IRPM (for adults) or 2) O2 saturation <93% or 3) No improvement in O2 saturation, despite oxygen supply or Arterial hypotension or 4) Changes in capillary filling time or 5) Changes in the level of consciousness or 6) Oliguria.
Exclusion criteria	Age <18 years Refuse to sign the Informed Consent Form Patient's decision that their involvement is not in their interest Severe known liver disease (eg cirrhosis, with aminotransferase levels> 5 times the reference value limit) Pregnancy or breastfeeding period Severe bacterial infection Severe diarrhea Diverticulitis or intestinal perforation Infection known as HIV Presence of one of the following uncontrolled or unstable cardiovascular diseases: stroke, ECG confirmed acute ischemia or myocardial infarction and / or clinically significant dysrhythmia Known history of gastrointestinal bleeding, uncontrolled peptic ulcer or uncontrolled duodenal ulcer Known history of hemophilia or other bleeding disorders History of organ transplantation, congenital immunodeficiency.
Interventions
	Treatment Ixekizumab 80 mg/ week subcutaneously, once a week for 4 weeks or until discharge. Interleukin-2 1.5 million IU/day subcutaneously for 7 days or until discharge. Colchicine Initial dose: 0.5 mg orally every 8 hours for 3 days - Maintenance dose: 0.5 mg orally twice daily for 4 weeks (+/-7 days)
	Control Standard care
Participants
	Randomized participants : Ixekizumab=16 Interleukin-2=14 Colchicine=14 Standard care=16
	Characteristics of participants N= 60 Mean age : NR 37 males Severity : Mild: n=0 / Moderate: n=37 / Severe: n=17 Critical: n=6 Number of vaccinated participants: 0
Primary outcome
	In the register Ordinal scale of seven World Health Organization (WHO) categories of IL-17 inhibitor versus low dose IL-2 versus indirect IL-6 inhibitor (colchicine) versus standard treatment in the treatment of severe COVID-19 [ Time Frame: On the 21st day of study, since inclusion. ] proportion of patients with clinical improvement, defined by an increase of two points in the ordinal scale of seven WHO categories
	In the report Proportion of patients with clinical improvement, defined by an increase of two points on the WHO’s ordinal scale at day 28.
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
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	Some concerns
General comment	In addition to the preprint and the published conference abstract, the study registry was used in data extraction and risk of bias assessment. Neither the protocol nor statistical analysis plan were available. There is no change from the trial registration in the intervention and control treatments. The timeframe for the registry primary outcome (21 days) does not reflect the reported timeframe for the primary outcome (28 days). Many outcomes from the registry are not reported in the abstract (e.g. need for mechanical ventilation). The preprint reports on an interim analysis and the study achieved the target sample size (n=60) specified in the trial registry. This study was updated on June 9th 2022 with data from the preprint.