Clinical trial NCT05563168: Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COVID-19
Keywords: Pneumonia, Viral
Diltiazem
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
Collaborators: name: Signia Therapeutics
First posted: 2022-10-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* 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

Primary outcomes:
measure: SARS-CoV-2 viral load decrease between D1 and D7
timeFrame: At day 1 and day 7 post treatment initiation.
Secondary outcomes:
measure: Time to clinical improvement
timeFrame: Within 28 days post-randomization
measure: Overall survival
timeFrame: at day 28
measure: SARS-CoV-2 viral load kinetics
timeFrame: Day 1, day 7, day 15, day 21 and day 28
measure: proportion of patients who are potential transfer candidates in intensive care
timeFrame: At Day 15
measure: Tolerance of the study treatment
timeFrame: Within 28 days after treatment initiation
measure: Duration of oxygen therapy
timeFrame: Within 28 days after treatment initiation
measure: Proportion of patients requiring assisted or non-invasive ventilation
timeFrame: Within 28 days after treatment initiation
measure: Duration of assisted or non-invasive ventilation
timeFrame: Within 28 days after treatment initiation
measure: Duration of hospitalization in intensive care unit
timeFrame: At day 28.
measure: Duration of hospitalization in intensive care unit
timeFrame: At day 90
measure: Hospital length of stay
timeFrame: At day 28.
measure: Hospital length of stay
timeFrame: At day 90
measure: Flow rate of oxygen used
timeFrame: Within 28 days after treatment initiation
measure: Extension of viral pneumonitis
timeFrame: Day 1, day 28
Other outcomes:
Locations:
city: Amiens
country: France
facility: respiratory department Amiens Hospital
city: Amiens
country: France
facility: Service de Maladies infectieuses et tropicales
city: Angers
country: France
facility: Département de Pneumologie, CHU Angers
city: Besançon
country: France
facility: Service de Pneumologie, CHU Besançon
city: Bordeaux
country: France
facility: Service de pneumologie Hôpital Haut-Leveque
city: Clermont-Ferrand
country: France
facility: Service de Pneumologie CHU Gabriel Montpied
city: Fort-de-France
country: France
facility: Service des Maladies Infectieuses et Tropicales
city: Grenoble
country: France
facility: Maladies infectieuses et Tropicales CHU Grenoble Rhône-Alpes
city: Lyon
country: France
facility: Departement of Pulmonology, Croix-Rousse Hospital, Hospices Civils de Lyon
city: Lyon
country: France
facility: Médecine Interne, Hôpital de la Croix- Rousse, HOSPICES CIVILS DE LYON
city: Marseille
country: France
facility: Clinique des bronches, de l'allergie et du sommeil Hôpital Nord
city: Montivilliers
country: France
facility: de Pneumologie Groupe Hospitalier du Havre Hôpital
city: Montpellier
country: France
facility: Pulmonology department CHU Montpellier
city: Paris
country: France
facility: Service Pneumologie, Hôpital BICHAT
city: Paris
country: France
facility: Service de Pneumologie, GHU APHP-Sorbonne Université, site Pitié Salpêtrière
city: Pierre-Bénite
country: France
facility: Service de pneumologie, CHLS, Hospices Civils de Lyon
city: Pierre-Bénite
country: France
facility: Médecine interne, CHMS, Hospices Civils de Lyon
city: Saint-Étienne
country: France
facility: Department of Pulmonology-Thoracic Oncology, University Hospital of SaintEtienne
city: Strasbourg
country: France
facility: Service de pneumologie, CHRU Strasbourg
city: Toulouse
country: France
facility: Clinique des Voies Respiratoires Hôpital Larrey
city: Tourcoing
country: France
facility: Service des Maladies Infectieuses et du Voyageur Hôpital Gustave Dron
Study officials:
affiliation: Departement of Pulmonology, Croix-Rousse Hospital, Hospices Civils de Lyon
name: Gilles Devouassoux, Pr
role: PRINCIPAL_INVESTIGATOR
References: