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DYNAMIC Study (DoxycYcliNe AMbulatoIre COVID-19) (DYNAMIC)

Primary Purpose

COVID19

Status
Withdrawn
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Doxycycline
Placebo
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID19

Eligibility Criteria

46 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU Avicenne - APHP
  • CHU Bordeaux
  • CHU Caen
  • CHU Dijon
  • CHU Grenoble
  • CHU Nantes

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Doxycycline 100mg

Doxycycline placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Percentage of Patients with Clinical Respiratory Aggravation
Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment
Percentage of patients hospitalized
Percentage of patients hospitalized after at least 48 hours of experimental treatment
Percentage of patients requiring ventilatory assistance
Percentage of patients requiring ventilatory assistance

Secondary Outcome Measures

Positive SARS-CoV-2 PCR Test
Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)
Duration of symptoms
Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)
Duration of hospitalization
Total duration of hospitalization
Hospitalization intensive care or reanimation
Duration of hospitalization in intensive care or reanimation
Duration of mechanical ventilatory assistance
Duration of mechanical ventilatory assistance
Percentage of deaths related to SARS-CoV-2
Percentage of deaths related to SARS-CoV-2 infection
AE / SAE in both arms
Number of AE / SAE in both arms

Full Information

First Posted
April 27, 2020
Last Updated
April 13, 2022
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04371952
Brief Title
DYNAMIC Study (DoxycYcliNe AMbulatoIre COVID-19)
Acronym
DYNAMIC
Official Title
Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Withdrawn
Why Stopped
withdrawal due to the evolution of the epidemic, the arrival of vaccination and because the associated centres could no longer commit to the number of inclusions requested
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
February 1, 2021 (Anticipated)
Study Completion Date
February 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double blind
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Doxycycline 100mg
Arm Type
Experimental
Arm Description
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
Arm Title
Doxycycline placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Intervention Description
comparison of doxycycline 200 mg/day to placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo : lactose, 380 mg/gélule
Primary Outcome Measure Information:
Title
Percentage of Patients with Clinical Respiratory Aggravation
Description
Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment
Time Frame
after at least 48 hours of treatment
Title
Percentage of patients hospitalized
Description
Percentage of patients hospitalized after at least 48 hours of experimental treatment
Time Frame
after at least 48 hours of experimental treatment
Title
Percentage of patients requiring ventilatory assistance
Description
Percentage of patients requiring ventilatory assistance
Time Frame
Day 0 to Day 28
Secondary Outcome Measure Information:
Title
Positive SARS-CoV-2 PCR Test
Description
Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)
Time Frame
Day -1 or day 0 AND Day 7
Title
Duration of symptoms
Description
Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)
Time Frame
Day 0 to Day 28
Title
Duration of hospitalization
Description
Total duration of hospitalization
Time Frame
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
Title
Hospitalization intensive care or reanimation
Description
Duration of hospitalization in intensive care or reanimation
Time Frame
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
Title
Duration of mechanical ventilatory assistance
Description
Duration of mechanical ventilatory assistance
Time Frame
to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0
Title
Percentage of deaths related to SARS-CoV-2
Description
Percentage of deaths related to SARS-CoV-2 infection
Time Frame
Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)
Title
AE / SAE in both arms
Description
Number of AE / SAE in both arms
Time Frame
Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
46 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
CHU Avicenne - APHP
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
CHU Bordeaux
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Facility Name
CHU Caen
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
CHU Dijon
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
CHU Grenoble
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CHU Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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DYNAMIC Study (DoxycYcliNe AMbulatoIre COVID-19)

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