Trial RBR-5s2mqg
Publication Mansour E, medRxiv, 2020 (preprint)
Dates: 4/23/2020 to 6/14/2020
Funding: Public/non profit (University of Campinas and Sao Paulo Research Foundation)
Conflict of interest: No

Methods
RCT
Blinding: Unblinded
Location : Single center / Brazil
Follow-up duration (days): 28
Inclusion criteriaInclusion criteria were age at least 18 years at the time of signing the consent form, symptom duration of 12 days or less upon recruitment, SARS-CoV-2 diagnosis by RT-PCR method according to the Berlin-Charite protocol 56, diagnosis of COVID-19 typical pneumonia confirmed by CT of the chest and scored by two lung expert radiologists, SpO2 ≤94% in ambient air or Pa02/FiO2 ≤300 mmHg, willingness of study participants to accept randomization to any assigned treatment arm, patient or responsible family member signing the consent form, and agreement that patient should not enroll in any other experimental study prior to completion of the 28-day follow-up.
Exclusion criteriaExclusion criteria were pregnant or breastfeeding women (a beta- HCG level was determined in all eligible women of childbearing age); severe renal impairment (estimated glomerular filtration rate ≤30 ml/min/1.73 m2), patients receiving continuous renal replacement therapy (hemodialysis or peritoneal dialysis), or previous renal transplant; severe liver disease (AST or ALT 5X above the reference value); HIV infection (HIV was tested for in all eligible patients); or patients with any other immunodeficiencies, previous diagnosis of cancer, previous diagnosis of hereditary angioedema, previous ischemic myocardial disease, previous thromboembolic disease,current use of immunosuppressive drug therapy, or use of any experimental treatment for SARS-CoV-2 infection within 30 days prior to screening.
Interventions
Treatment 1
Icatibant (30mg/NA)
Co-Intervention: Standard care
Duration : 4 days
Control
Standard care (NA/NA)
Co-Intervention: Standard care
Duration : NA
Treatment 3
C1 Esterase/Kallikrein Inhibitor (20IU/kg/NA)
Co-Intervention: Standard care
Duration : 2 days, D1 and D4
Participants
Randomized
30 participants n1=10/ n2=10/ n3=10
Characteristics of participants
N=30
Mean age : 51.6
16 males
Severity : Mild: n=0 / Moderate: n=0/ Severe: n=30 Critical: n=0
Primary outcome
In the register
Time to clinical improvement (TTCI), which refers to the time from randomization to an improvement of two points on the seven-category ordinal scale stated below or live discharge from the hospital: 1. not hospitalized with a resumption of normal activities; 2. not hospitalized, but unable to resume normal activities; 3. hospitalized, not requiring supplemental oxygen; 4. hospitalized, requiring supplemental oxygen; 5. hospitalized, requiring nasal high-flow oxygen therapy or non-invasive mechanical ventilation;
In the report
Time to clinical improvement (TTCI) as defined by the Cap-China Network.
Documents
available

Protocol

NR

Statistical plan

NA

Data-sharing stated

Yes
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 all available versions of the pre-print article, the study registry was used in data extraction and risk of bias assessment. This is the report for a proof of concept study however the trial registry for this study reflects a Phase 2/3 RCT with a target sample size of 180 participants. This study did not achieve the target sample size reported in the registry. There is no change from the trial registration in the intervention and control treatments. No protocol or pre-specified statistical analysis plan are available. There is no change from the trial registration in the primary and most secondary outcomes. One secondary outcome (occurrence of acute kidney injury) is reported in the registry and not in the pre-print. The primary outcome, TTCI is not reported, neither are the secondary outcomes of clinical status at D7, D14, D21 based on the TTCI scale.