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

NCT05563168 | Withdrawn Phase 2 DMC

• 2 other identifiers: 69HCL21_08552021-004160-94
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 21

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.

Conditions

COVID-19

Keywords

Pneumonia, Viral; Diltiazem

Outcome Measures

Primary Outcomes (1)

• SARS-CoV-2 viral load decrease between D1 and D7

  Dosage of the standardized SARS-CoV-2 viral load on nasopharyngeal samples on day 1 and day 7 after treatment initiation.

  At day 1 and day 7 post treatment initiation.

Secondary Outcomes (14)

• Time to clinical improvement

  Within 28 days post-randomization

• Overall survival

  at day 28

• SARS-CoV-2 viral load kinetics

  Day 1, day 7, day 15, day 21 and day 28

• proportion of patients who are potential transfer candidates in intensive care

  At Day 15

• Tolerance of the study treatment

  Within 28 days after treatment initiation

Study Arms (2)

Standard Of Care (SOC) + diltiazem

EXPERIMENTAL

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.

Drug: DILTIAZEM TEVA 60 mg or placebo

SOC + placebo

PLACEBO COMPARATOR

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

Drug: DILTIAZEM TEVA 60 mg or placebo

Interventions

DILTIAZEM TEVA 60 mg or placebo DRUG

DILTIAZEM TEVA 60 mg 3 times a day during 7 days + standard of care Or placebo 3 times a day during 7 days + standard of care.

SOC + placebo; Standard Of Care (SOC) + diltiazem

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 or over
• 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.

You may not qualify if:

• Patient with cognitive impairment, at the discretion of the investigator
• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead
• Signia Therapeutics: collaborator

Study Sites (21)

respiratory department Amiens Hospital

Amiens, 80054, France

Location

Service de Maladies infectieuses et tropicales

Amiens, 80054, France

Location

Département de Pneumologie, CHU Angers

Angers, 49100, France

Location

Service de Pneumologie, CHU Besançon

Besançon, 25030, France

Location

Service de pneumologie Hôpital Haut-Leveque

Bordeaux, 33604, France

Location

Service de Pneumologie CHU Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

Service des Maladies Infectieuses et Tropicales

Fort-de-France, 97261, France

Location

Maladies infectieuses et Tropicales CHU Grenoble Rhône-Alpes

Grenoble, 38043, France

Location

Departement of Pulmonology, Croix-Rousse Hospital, Hospices Civils de Lyon

Lyon, 69004, France

Location

Médecine Interne, Hôpital de la Croix- Rousse, HOSPICES CIVILS DE LYON

Lyon, 69004, France

Location

Clinique des bronches, de l'allergie et du sommeil Hôpital Nord

Marseille, 13015, France

Location

de Pneumologie Groupe Hospitalier du Havre Hôpital

Montivilliers, 76290, France

Location

Pulmonology department CHU Montpellier

Montpellier, 34295, France

Location

Service Pneumologie, Hôpital BICHAT

Paris, 75018, France

Location

Service de Pneumologie, GHU APHP-Sorbonne Université, site Pitié Salpêtrière

Paris, 75651, France

Location

Service de pneumologie, CHLS, Hospices Civils de Lyon

Pierre-Bénite, 69310, France

Location

Médecine interne, CHMS, Hospices Civils de Lyon

Pierre-Bénite, France

Location

Department of Pulmonology-Thoracic Oncology, University Hospital of SaintEtienne

Saint-Etienne, 42055, France

Location

Service de pneumologie, CHRU Strasbourg

Strasbourg, 67000, France

Location

Clinique des Voies Respiratoires Hôpital Larrey

Toulouse, 31059, France

Location

Service des Maladies Infectieuses et du Voyageur Hôpital Gustave Dron

Tourcoing, 59208, France

Location

MeSH Terms

Conditions

COVID-19; Pneumonia, Viral

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Gilles Devouassoux, Pr

  Departement of Pulmonology, Croix-Rousse Hospital, Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 3, 2022
• Study Start: April 1, 2023
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: May 26, 2023

Record last verified: 2023-05

Locations

FR (21)