Covid-19 Living Data

Trial NCT04794803; EudraCT 2020-001645-40
Publication Landoni G, Infect Dis Ther (2022) (published paper)
Dates: 2020-05-05 to 2020-10-30
Funding: Private (Dompe´ Farmaceutici SpA, Milan, Italy. Dompe´ Farmaceutici SpA participated in the design and conduct of the study; management, analysis, and interpretation of the data; preparation and review of the manuscript; and provided funding for the journal’s Rapid Service Fee.)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Brazil, Italy Follow-up duration (days): 28
Inclusion criteria	Hospitalized adults (aged 18–90 years old) polymerase chain reaction-confirmed COVID-19 diagnosis and severe pneumonia respiratory distress [respiratory rate ≥30 breaths/ minute without oxygen)] and/or partial arterial oxygen pressure (PaO2)/fraction of inspiration O2 (FiO2) >100 to <300 mmHg (1 mmHg = 0.133 kPa) Lung involvement confirmed via chest imaging, consistent with pneumonia elevated inflammatory markers with at least one of the following - lactate dehydrogenase > normal range, C-reactive protein ≥100 mg/L, or IL-6 ≥40 pg/mL, serum ferritin ≥900 ng/mL, serum crosslinked fibrin >20 lg/mL.
Exclusion criteria	Could not provide informed consent had severe hepatic dysfunction (Child–Pugh score ≥C, or aspartate aminotransferase >5 times the upper limit) severe renal dysfunction (estimated glomerular filtration rate ≤30 mL/min/ 1.73 m2), or received continuous renal replacement therapy, hemodialysis, or peritoneal dial- ysis hypersensitivity to ibuprofen or to more than one non-steroidal anti-inflammatory drug (NSAID) or more than one sulfonamide medication (hypersensitivity to sulfanilamide antibiotics alone, e.g., sulfamethoxazole, did not qualify for exclusion) were excluded severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within one month before enrollment were excluded at risk for complications from NSAID use because one of reparixin’s metabolites is ibuprofen pregnant and lactating women and those planning to get pregnant participating in other interventional clinical trials not in a clinical condition compatible with the oral administration of the study drug.
Interventions
	Treatment Reparixin 1200 mg orally three times a day for 7-21 days.
	Control Standard care
Participants
	Randomized participants : Standard care=19 Reparixin=37
	Characteristics of participants N= 56 Mean age : NR 42 males Severity : Mild: n=0 / Moderate: n=25 / Severe: n=30 Critical: n=0 Number of vaccinated participants: 0
Primary outcome
	In the register Percentage of Participants With Composite Endpoint of Clinical Events [ Time Frame: Up to Day 1 ] Composite event is defined as the onset of at least one of the following events: supplemental oxygen requirement based on a worsening of PaO2/FiO2 ratio, invasive mechanical ventilation use, admission to Intensive Care Unit (ICU), use of a rescue medication for any reason.
	In the report Time-to-event analysis of the composite endpoint of clinical events. The composite endpoint was defined as patients requiring at least one of the following at any time during treatment or follow-up: supplemental oxygen, based on deterioration of the PaO2/FiO2 ratio by at least one-third (− 33.3%) from baseline PaO2/FiO2, mechanical ventilation use, admission to ICU, and/or use of a rescue medication for any reason.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: 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	High
General comment	In addition to the published article, the trial registries, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. The composite primary outcome was a time-to-event outcome in the article but a proportion in the registry. The primary and secondary outcomes were altered in the registry during the course of the study, but overall reflect those in the first version of the registration. The trial (n = 56) achieved the target sample size stated in the protocol and report (n = 48). The study had a high rate of non-completion.