Clinical trial NCT04371952: DYNAMIC Study (DoxycYcliNe AMbulatoIre COVID-19)
Official title: Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: COVID19
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2020-05-01
Enrollment: 0
Sex: ALL
Minimum age (years): 46
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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:

  * 70 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.

Exclusion Criteria:

* Lactose-intolerant patients
* Patient needing immediate hospitalization for any medical reason
* Patient having more than 5 days of clinical symptoms at the inclusion visit
* 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

Primary outcomes:
measure: Percentage of Patients with Clinical Respiratory Aggravation
timeFrame: after at least 48 hours of treatment
measure: Percentage of patients hospitalized
timeFrame: after at least 48 hours of experimental treatment
measure: Percentage of patients requiring ventilatory assistance
timeFrame: Day 0 to Day 28
Secondary outcomes:
measure: Positive SARS-CoV-2 PCR Test
timeFrame: Day -1 or day 0 AND Day 7
measure: Duration of symptoms
timeFrame: Day 0 to Day 28
measure: Duration of hospitalization
timeFrame: 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
measure: Hospitalization intensive care or reanimation
timeFrame: 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
measure: Duration of mechanical ventilatory assistance
timeFrame: to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0
measure: Percentage of deaths related to SARS-CoV-2
timeFrame: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)
measure: AE / SAE in both arms
timeFrame: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)
Other outcomes:
Locations:
city: Bobigny
country: France
facility: CHU Avicenne - APHP
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Caen
country: France
facility: CHU Caen
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: Nantes
country: France
facility: CHU Nantes
Study officials:
References: