Multicenter, Double-blind, Randomized, Placebo-controlled Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia - A Phase IIB, Proof of Concept Study
Overview
- Phase
- Phase 2
- Intervention
- DILTIAZEM TEVA 60 mg or placebo
- Conditions
- COVID-19
- Sponsor
- Hospices Civils de Lyon
- Locations
- 21
- Primary Endpoint
- SARS-CoV-2 viral load decrease between D1 and D7
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
Brief Summary
SARS-CoV-2 infection is responsible for hypoxemic pneumonia, which is sometimes serious and associated with excess mortality. To date, with the exception of dexamethasone, which has shown clinical efficacy by reducing the mortality of infected patients, no other therapeutic strategy has demonstrated a curative clinical benefit, particularly in the initial stages facilitating viral eviction. .
Based on the mechanism of action and the available data, diltiazem, administered in the first days post-infection, could facilitate viral eradication in these patients through the stimulation of the innate immune response of cells of the infected respiratory epithelium, actor in the fight against SARS-CoV-2.
In this context, the investigators propose the DICOV trial, to demonstrate the ability of diltiazem to reduce the viral load more rapidly, in patients hospitalized for COVID-19 hypoxemic pneumonia.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female aged 18 or over
- •SARS-CoV-2 infection proven by RT-PCR on a nasopharyngeal sample within 72 hours prior to inclusion in the study
- •Onset of symptoms of viral infection ≤ 7 days
- •Hospitalization required due to hypoxemia (air saturation \< 94% at rest)
- •Presence of radiological pneumopathy (chest X-ray or non-enhanced thoracic CT)
- •Patient affiliated to a social security scheme.
- •Patient capable of giving free, informed and written consent.
- •Patient with a history of SARS-CoV-2 infection may participate in the study, but this infection must not have occurred within the 3 months prior to his current hospitalization.
- •Patient who has been vaccinated against SARS-CoV-2 can participate in the study (regardless of the number of doses)
- •Patient not eligible for specific anti-COVID treatment authorized in France (MA or early access) and not part of the standard of care at the time of the study
Exclusion Criteria
- •Need for hospitalization in intensive care unit at inclusion
- •Patient with cognitive impairment, at the discretion of the investigator
- •Pregnant woman (positive urine pregnancy test on inclusion) or breastfeeding
- •Participation in another interventional study or being in the exclusion period from a previous study
- •Patient on diltiazem therapy
- •Contraindication to diltiazem
- •Hypersensitivity to diltiazem or to any of the excipients
- •Unaided sinus dysfunction
- •Unaided 2nd and 3rd degree atrioventricular blocks
- •Left ventricular failure with pulmonary stasis (cardiogenic edema)
Arms & Interventions
Standard Of Care (SOC) + diltiazem
Patients will receive the standard of care at the time of their inclusion in the trial and will also receive diltiazem (60mg 3 times a day) for 7 days.
Intervention: DILTIAZEM TEVA 60 mg or placebo
SOC + placebo
Patients will receive the standard of care at the time of their inclusion in the trial and will also receive a diltiazem placebo (3 times a day) for 7 days
Intervention: DILTIAZEM TEVA 60 mg or placebo
Outcomes
Primary Outcomes
SARS-CoV-2 viral load decrease between D1 and D7
Time Frame: At day 1 and day 7 post treatment initiation.
Dosage of the standardized SARS-CoV-2 viral load on nasopharyngeal samples on day 1 and day 7 after treatment initiation.
Secondary Outcomes
- Time to clinical improvement(Within 28 days post-randomization)
- Overall survival(at day 28)
- proportion of patients who are potential transfer candidates in intensive care(At Day 15)
- Duration of assisted or non-invasive ventilation(Within 28 days after treatment initiation)
- Duration of hospitalization in intensive care unit(At day 90)
- SARS-CoV-2 viral load kinetics(Day 1, day 7, day 15, day 21 and day 28)
- Flow rate of oxygen used(Within 28 days after treatment initiation)
- Extension of viral pneumonitis(Day 1, day 28)
- Tolerance of the study treatment(Within 28 days after treatment initiation)
- Duration of oxygen therapy(Within 28 days after treatment initiation)
- Proportion of patients requiring assisted or non-invasive ventilation(Within 28 days after treatment initiation)
- Hospital length of stay(At day 90)