Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia (DICOV)

Civil Hospices of Lyon

Status and phase: Withdrawn; Phase 2

Conditions: COVID-19

Treatments: Drug: DILTIAZEM TEVA 60 mg or placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05563168

2021-004160-94 (EudraCT Number)

69HCL21_0855

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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
• Female patient of childbearing age using effective contraception during study participation, the same applies to partners of childbearing age of male patients. Male patients must use condoms.

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)
  • Severe bradycardia (≤ 40 beats per minute)
  • In combination with: dantrolene infusion, pimozide, dihydroergotamine, ergotamine, nifedipine, ivabradine, beta blockers, antiarrhythmics, esmolol, fingolimod.

• Patient with renal, hepatic or cardiac insufficiency (at the discretion of the investigator)

• Hypersensitivity to mannitol

• Use of anti-COVID medications other than those offered in routine testing and care.

• Presence of hemodynamic instability, systolic blood pressure < 100 mmHg, presence of multi-visceral failure

• Prior respiratory pathology requiring oxygen therapy at the long-term and/or non-invasive ventilation

• Immunocompromised patients (organ transplant, allograft, under chemotherapy, under Rituximab or a history of Rituximab), for any other situation seek the advice of the coordinating investigator

• Patient under guardianship, curatorship or safeguard of justice

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Standard Of Care (SOC) + diltiazem

Experimental group

Description:

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.

Treatment:

Drug: DILTIAZEM TEVA 60 mg or placebo

SOC + placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: DILTIAZEM TEVA 60 mg or placebo