Effectiveness and Safety of Medical Treatment for SARS-CoV-2 (COVID-19) in Colombia
Status:
Completed
Trial end date:
2021-06-30
Target enrollment:
Participant gender:
Summary
Introduction: The COVID-19 pandemic is characterized by significant morbidity and mortality.
Treatments have been administered to patients with COVID-19 in order to control viral
infection, among them: Hydroxychloroquine (HCQ), Lopinavir/Ritonavir (Lop/r), Remdesivir,
Favipavir, Emtricitabine/ Tenofovir acting over bacterial co-infection Azithromycin
(Azithro), or modifying the inflammatory response of the host (Tocilizumab, colchicine,
dexamethasone, and by other mechanisms (rosuvastatin). Except for dexamethasone clinical
trials offer conflicting evidence regarding the effectiveness and safety of therapies.
Objective: Evaluate the effectiveness and safety of pharmacological therapies used to treat
adult patients with COVID-19.
Methods: Pragmatic randomized controlled trial. Study population: Adults aged 18 years or
over with a positive real-time polymerase chain reaction (RT-PCR) or with high suspicion of
Severe Acute Respiratory Syndrome CoV-2 (SARS CoV-2) and diagnosis of mild, severe or
critical pneumonia, requiring hospital management at six hospitals in Colombia. Exclusion
criteria: Pregnancy, known allergy to treatment, cirrhosis or hepatic abnormality
(transaminases greater than 5 reference values), glomerular filtration rate lesser than 30
ml/min/1.73m^2, history of lung fibrosis, advanced or metastatic cancer. A sample size was
calculated from a sensitivity analysis with three scenarios:
scenario 1 a total of 1,163 patients, that is, 291 per treatment arm with alpha of Alpha =
0.05; power 0.8; Prop1 = 0.2 and Prop2 = 0.1 (expected difference of 10%) and 10% of possible
losses,scenario 2. With the previous parameters and with a Prop1 = 0.15 and Prop2 = 0.05 for
a total of 814 patients (204 per arm of treatment). scenario 3. With Alpha = 0.1, Prop1 =
0.15 and Prop2 = 0.05, the other previous parameters, for a total of 686 patients (172 per
treatment). in scenario 1 the study will be carried out in two phases. The first phase will
be conducted with 400 participants and aims to identify treatments with higher or minimum
potential, discontinue treatments with higher toxicity, and have the opportunity of
introducing new treatments with potential efficacy. The second phase will be conducted with
1,163 participants to evaluate the effectiveness of the selected treatments.
Four interventions have been defined: I1 Emtricitabine/ teneofovir , I2 Colchicine plus
rosuvastatin, I3 Emtricitabine/ teneofovir plus Colchicine plus rosuvastatin and I4 standard
treatment. Within each institution, participants will be randomly assigned to one of the
treatment arms assigned to that institution. Concealment will be kept through software that
maintain the assignment concealed until the random assignment is done . Treatment
administration will be open. Variables: Sociodemographic and clinical at recruitment;
(comorbidities, need for therapeutic support , grade of invasion at admission). Primary
outcomes. Effectiveness: Mortality. Safety: Serious adverse events (AE) assessed by the NCI
Community Oncology Research Program (NCORP) Guidance for Collection of Adverse Events Related
to COVID-19 Infection. Secondary outcomes: Intensive care unit (ICU) admission, requirement
of respiratory support, time to death, number of participants cured, any adverse event
related to treatment.
Analysis: Descriptive for the presentation of summary measures of the basal conditions by
type of variable. Bivariate. Description of the basal conditions (with organic failure at
admission, without failure at admission), by type of treatment, by participating institution.
Description of crude effectiveness and safety by means of the difference of accumulated
incidences, each one with 95% confidence intervals (95% CI) Intention to treat analyisis will
be done. Adjusted analysis: The ratio and difference of cumulative incidences of mortality at
7 and 28 days and severe adverse events between treatments will be estimated, adjusting for
confounding variables using logistic regression models with mixed effects considering each
institution as a level or from equations. generalized estimation (GEE). On the other hand, as
part of the pragmatic approach, the surface under cumulative ranking curve (SUCRA) will be
calculated based on Bayesian theory to define which drug has the highest probability of being
the most useful in the management of infection.
Ethical considerations: The study has a risk beyond minimum according to the Resolution
8430/1993 of the Colombian Ministry of Health. Informed consent will be explained and signed
if the patient is in condition to do so. This protocol will undergo evaluation by the ethics
committee at each of the participating institutions and at the National University of
Colombia. The protocol follows the Helsinki Declaration and institutional protocols for
clinical investigation.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Universidad Nacional de Colombia
Collaborators:
Clínica Colsanitas-Clínica Universitaria Colombia Clínica Infantil Santa María del Lago Clínica Reina Sofía Clínica Universitaria Colombia Fundación Cardio Infantil Fundación Cardioinfantil Instituto de Cardiología Hospital Universitario de Neiva Hospital Universitario Nacional de Colombia Hospital Universitario Nacional de Colombia (HUN) Hospital Universitario San Ignacio Pontificia Universidad Javeriana