DYNAMIC Study (DoxycYcliNe AMbulatoIre COVID-19)

NCT04371952 | Withdrawn Phase 3 DMC

• 1 other identifier: RC20_0191
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief Summary

The aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of reducing or even abolishing the cytokine explosion and thus the evolution towards a serious form of the disease which can lead to death. Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival. Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may also be able to inhibit the replication of positive-polarity single-stranded RNA viruses, such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property used in the treatment of inflammatory skin diseases for many years. These modulating effects are noted on several targets of innate immunity: They can decrease the expression of NFKB, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and free radical release. Tetracyclines could therefore participate in limiting the cytokine release induced by COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to inhibit viral replication.

Conditions

COVID19

Outcome Measures

Primary Outcomes (3)

• Percentage of Patients with Clinical Respiratory Aggravation

  Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment

  after at least 48 hours of treatment

• Percentage of patients hospitalized

  Percentage of patients hospitalized after at least 48 hours of experimental treatment

  after at least 48 hours of experimental treatment

• Percentage of patients requiring ventilatory assistance

  Percentage of patients requiring ventilatory assistance

  Day 0 to Day 28

Secondary Outcomes (7)

• Positive SARS-CoV-2 PCR Test

  Day -1 or day 0 AND Day 7

• Duration of symptoms

  Day 0 to Day 28

• Duration of hospitalization

  From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

• Hospitalization intensive care or reanimation

  From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

• Duration of mechanical ventilatory assistance

  to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0

Study Arms (2)

Doxycycline 100mg

EXPERIMENTAL

Doxycycline capsule containing 2 tablets doxycycline 100mg over-encapsulated. Doxycycline is given at 200 mg once a day and administered per os during 2 weeks

Drug: Doxycycline

Doxycycline placebo

PLACEBO COMPARATOR

Doxycycline Placebo capsule 200 mg, containing 1 capsule of a marketed placebo = RODAEL placebo ( lactose, 380 mg / capsule). Doxycycline placebo is given once a day and administered per os during 2 weeks

Drug: Placebo

Interventions

Doxycycline DRUG

comparison of doxycycline 200 mg/day to placebo

Doxycycline 100mg

Placebo DRUG

Placebo : lactose, 380 mg/gélule

Doxycycline placebo

Eligibility Criteria

• Age: 46 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman \> 45 years old.
• Patient with a positive SARS-CoV-2 PCR
• Patient with ENT and / or respiratory symptoms, without hospitalization criteria (no dyspnea, respiratory rate \<22 / min, SaO2 ≥ 94% in ambient air), or digestive signs.
• Patient with at least one of the following risk factors for unfavorable outcome:
• years, BMI\> 30, cardiovascular history (stroke, coronary artery disease, complicated hypertension, cardiac surgery, NYHA III or IV heart failure), respiratory pathology likely to decompensate during viral infection respiratory failure, unbalanced and / or complicated diabètes, respiratory pathology likely to decompensate in the event of of viral infection, patients with renal insufficiency chronic dialysis, .cancer patients under treatment.

You may not qualify if:

• Lactose-intolerant patients
• Patient needing immediate hospitalization for any medical reason
• Patients with a history of allergy to tetracyclines
• Pregnant or lactating women
• Patients participating in another clinical trial
• Patients with photosensitive skin pathology
• Patients treated with anticoagulant
• Patients treated with oral retinoids: isotretinoin, alitretinoin, acitretin
• Patients treated with vitamin A Patients treated with systemic antibiotics for the duration of treatment
• Patients treated with barbiturates, carbamazepine or phenytoin
• Patients with treatment that may have an effect on COVID-19 infection: chloroquine, hydroxychloroquine, remdesivir, ganciclovir, acyclovir, ribavirin, lopinavir-ritonavir
• Patients under guardianship or trusteeship or in safeguard of justice

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (6)

CHU Avicenne - APHP

Bobigny, 93009, France

Location

CHU Bordeaux

Bordeaux, 33075, France

Location

CHU Caen

Caen, 14033, France

Location

CHU Dijon

Dijon, 21079, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

CHU Nantes

Nantes, 44093, France

Location

MeSH Terms

Conditions

COVID-19

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: May 1, 2020
• Study Start: February 1, 2021
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)