Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia
- Registration Number
- NCT05563168
- Lead Sponsor
- Hospices Civils de Lyon
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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.
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Need for hospitalization in intensive care unit at inclusion
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Patient with cognitive impairment, at the discretion of the investigator
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Pregnant woman (positive urine pregnancy test on inclusion) or breastfeeding
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Participation in another interventional study or being in the exclusion period from a previous study
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Patient on diltiazem therapy
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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.
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Patient with renal, hepatic or cardiac insufficiency (at the discretion of the investigator)
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Hypersensitivity to mannitol
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Use of anti-COVID medications other than those offered in routine testing and care.
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Presence of hemodynamic instability, systolic blood pressure < 100 mmHg, presence of multi-visceral failure
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Prior respiratory pathology requiring oxygen therapy at the long-term and/or non-invasive ventilation
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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
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Patient under guardianship, curatorship or safeguard of justice
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard Of Care (SOC) + diltiazem DILTIAZEM TEVA 60 mg or placebo 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. SOC + placebo DILTIAZEM TEVA 60 mg or 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
- Primary Outcome Measures
Name Time Method SARS-CoV-2 viral load decrease between D1 and D7 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 Outcome Measures
Name Time Method Time to clinical improvement Within 28 days post-randomization Time to clinical improvement (in days), defined as the time from randomization to an improvement of at least 2 points on a 7-point ordinal scale
Overall survival at day 28 Percentage of patients who died between D1 and D28 of the start of treatment
proportion of patients who are potential transfer candidates in intensive care At Day 15 Percentage of patients candidates for transfer to intensive care at Day 15 of the start of treatment
Duration of assisted or non-invasive ventilation Within 28 days after treatment initiation Number of days the patient was put on assisted or non-invasive ventilation
Duration of hospitalization in intensive care unit At day 90 Number of days spent in intensive care. For patients still in intensive care on D28 this information will be collected on D90
SARS-CoV-2 viral load kinetics Day 1, day 7, day 15, day 21 and day 28 Kinetics of viral load decrease by dosage of the normalized SARS-CoV-2 viral load on nasopharyngeal samples
Flow rate of oxygen used Within 28 days after treatment initiation Maximum oxygen rate used
Extension of viral pneumonitis Day 1, day 28 Difference in extension of viral pneumonitis on comparative analysis scans performed at D1 and D28
Tolerance of the study treatment Within 28 days after treatment initiation Occurrence of adverse events, severe adverse events and premature discontinuation of study treatment
Duration of oxygen therapy Within 28 days after treatment initiation Number of days the patient was put on oxygen therapy
Proportion of patients requiring assisted or non-invasive ventilation Within 28 days after treatment initiation Percentage of patients requiring assisted or non-invasive ventilation
Hospital length of stay At day 90 Number of days spent in hospital. For patients still in intensive care on D28 this information will be collected on D90
Trial Locations
- Locations (21)
Service des Maladies Infectieuses et Tropicales
🇫🇷Fort-de-France, France
respiratory department Amiens Hospital
🇫🇷Amiens, France
Service de Maladies infectieuses et tropicales
🇫🇷Amiens, France
Département de Pneumologie, CHU Angers
🇫🇷Angers, France
Clinique des bronches, de l'allergie et du sommeil Hôpital Nord
🇫🇷Marseille, France
Service de pneumologie Hôpital Haut-Leveque
🇫🇷Bordeaux, France
Service de Pneumologie, CHU Besançon
🇫🇷Besançon, France
Service de Pneumologie CHU Gabriel Montpied
🇫🇷Clermont-Ferrand, France
Departement of Pulmonology, Croix-Rousse Hospital, Hospices Civils de Lyon
🇫🇷Lyon, France
Médecine Interne, Hôpital de la Croix- Rousse, HOSPICES CIVILS DE LYON
🇫🇷Lyon, France
Maladies infectieuses et Tropicales CHU Grenoble Rhône-Alpes
🇫🇷Grenoble, France
de Pneumologie Groupe Hospitalier du Havre Hôpital
🇫🇷Montivilliers, France
Service Pneumologie, Hôpital BICHAT
🇫🇷Paris, France
Pulmonology department CHU Montpellier
🇫🇷Montpellier, France
Service de Pneumologie, GHU APHP-Sorbonne Université, site Pitié Salpêtrière
🇫🇷Paris, France
Médecine interne, CHMS, Hospices Civils de Lyon
🇫🇷Pierre-Bénite, France
Service de pneumologie, CHLS, Hospices Civils de Lyon
🇫🇷Pierre-Bénite, France
Department of Pulmonology-Thoracic Oncology, University Hospital of SaintEtienne
🇫🇷Saint-Étienne, France
Service de pneumologie, CHRU Strasbourg
🇫🇷Strasbourg, France
Service des Maladies Infectieuses et du Voyageur Hôpital Gustave Dron
🇫🇷Tourcoing, France
Clinique des Voies Respiratoires Hôpital Larrey
🇫🇷Toulouse, France