DYNAMIC Study (DoxycYcliNe AMbulatoIre COVID-19)

COVID19 Clinical Trial

— DYNAMIC  

Official title:

Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04371952
• Other study ID #: RC20_0191
• Status: Withdrawn
• Phase: Phase 3
• Start date: February 1, 2021
• Est. completion date: February 1, 2021

Study information

• Verified date: April 2022
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 46 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• COVID19

Intervention

Drug:
• Doxycycline
comparison of doxycycline 200 mg/day to placebo
• Placebo
Placebo : lactose, 380 mg/gélule

Locations

Country	Name	City	State
France	CHU Avicenne - APHP	Bobigny
France	CHU Bordeaux	Bordeaux
France	CHU Caen	Caen
France	CHU Dijon	Dijon
France	CHU Grenoble	Grenoble
France	CHU Nantes	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of patients hospitalized	Percentage of patients hospitalized after at least 48 hours of experimental treatment	after at least 48 hours of experimental treatment
Primary	Percentage of patients requiring ventilatory assistance	Percentage of patients requiring ventilatory assistance	Day 0 to Day 28
Secondary	Positive SARS-CoV-2 PCR Test	Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)	Day -1 or day 0 AND Day 7
Secondary	Duration of symptoms	Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)	Day 0 to Day 28
Secondary	Duration of hospitalization	Total 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
Secondary	Hospitalization intensive care or reanimation	Duration of hospitalization in 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
Secondary	Duration of mechanical ventilatory assistance	Duration of mechanical ventilatory assistance	to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0
Secondary	Percentage of deaths related to SARS-CoV-2	Percentage of deaths related to SARS-CoV-2 infection	Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)
Secondary	AE / SAE in both arms	Number of AE / SAE in both arms	Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)