Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 6
- 主要终点
- Percentage of Patients with Clinical Respiratory Aggravation
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 46 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Doxycycline 100mg
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
干预措施: Doxycycline (Drug)
Doxycycline placebo
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
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Patients with Clinical Respiratory Aggravation
时间窗: after at least 48 hours of treatment
Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment
Percentage of patients hospitalized
时间窗: after at least 48 hours of experimental treatment
Percentage of patients hospitalized after at least 48 hours of experimental treatment
Percentage of patients requiring ventilatory assistance
时间窗: Day 0 to Day 28
Percentage of patients requiring ventilatory assistance
次要结局
- Positive SARS-CoV-2 PCR Test(Day -1 or day 0 AND Day 7)
- 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)
- AE / SAE in both arms(Day 28, or end of hospitalization if any (assessed up to 3 months after Day0))
- Percentage of deaths related to SARS-CoV-2(Day 28, or end of hospitalization if any (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)
- Duration of symptoms(Day 0 to Day 28)