Efficacy of HYdroxychloroquine and DILtiazem-nIClosamide Combination for the Treatment of Non-severe Forms of SARS-CoV2 Infection in Patients With Co-morbidities: Multicenter, Randomized, Open-labeled Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 主要终点
- death
研究概览
简要总结
No optimal antiviral intervention has been yet validated to treat COVID-19 disease. Comorbidities, such as older age, obesity, diabetes, history of cardiovascular diseases are associated with poor prognosis.
This study aims to evaluate the efficacy of two experimental antiviral treatments, compared to standard of care (SOC), to prevent clinical worsening, hospitalization or death at day 14 in adults with documented SARS-CoV-2 infection, asymptomatic or with symptoms lasting less than 8 days, and associated comorbidities without any severity criteria of the disease at inclusion.
Participants will be randomized to receive SOC alone or SOC + hydroxychloroquine 200 mg three times a day during 10 days or SOC + association of niclosamide 2 g at J1 then 500 mg two times a day with diltiazem 60 mg three times a day during 10 days. Efficacy and tolerance of each treatments will be compared across the three treatment groups during the 28 days of follow-up.
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
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Positive SARS-CoV-2 test on nasopharyngeal swab
- •Onset of symptoms <8 days prior to randomization
- •NEWS score<4 AND no item ≥2
- •At least one comorbidity among: age ≥ 70 years old, history of cardiac disease, diabetes, obesity, chronic kidney disease, chronic respiratory failure, immunosuppression, neoplasia, liver failure (stage ≥ Child-Pugh B)
- •Fully able to understand the challenges of the trial
- •Signed informed consent
- •Covered by Health Insurance
排除标准
- •For all patients:
- •Inability to decide to participate
- •Pregnancy or breath feeding
- •Hypersensitivity to any of the test drugs
- •stage 4 or 5 chronic kidney disease (DFG <30 mL/min/1.73 m²)
- •For hydroxychloroquine arm:
- •Long QT syndrome or QTc space >500 ms
- •Treatment with piperazine, halofantrine, dasatinib, nilotinib, citalopram, escitalopram, hydroxyzine, domperidone
- •Hepatic porphyria, retinopathy, known glucose-6-phosphate dehydrogenase deficiency,
- •Heart rate <50/min
- •hypokaliemia < 3.5 mmol/L
- •For diltiazem arm:
- •Heart rate<40/min
- •Sinus bradycardia, second- or third-degree atrioventricular block
- •Left heart insufficiency with pulmonary stasis
- •Treatment with dantrolene, pimozide, dihydroergotamine, ergotamine, nifedipine, ivabradine, esmolol, bêta-blockers (bisoprolol, carvedilol, metoprolol, nebivolol), fingolimod
研究组 & 干预措施
standard of care (SOC)
干预措施: Standard of care (SOC) (Other)
SOC + Hydroxychloroquine
干预措施: Standard of care (SOC) (Other)
SOC + Hydroxychloroquine
干预措施: Hydroxychloroquine (Drug)
SOC + Diltiazem-Niclosamide
干预措施: Standard of care (SOC) (Other)
SOC + Diltiazem-Niclosamide
干预措施: Association of diltiazem and niclosamide (Drug)
结局指标
主要结局
death
时间窗: At day 14
Composite criteria
Assisted-ventilation and/or hospitalization (composite criteria)
时间窗: At day 14
clinical worsening (composite criteria)
时间窗: At day 14
clinical worsening defined by at least one of the NEWS score item \> 2 (temperature \>39,1°C or\<35°C, cardiac rate \>111 or ≤40 bpm, respiratory rate \> 21 or ≤8 cycles par minute, SaO2 ≤ 93% room air (if its measure is available),need of oxygen
次要结局
- adverse drug reactions(during study, up to 28 days)
- cumulative incidence of hospitalizations(at day 14)
- cumulative incidence of viral shedding on SARS-CoV-2 rt-PCR on nasopharyngeal swab;(at day 3, day 8)
- National Early Warning Score (NEWS)(at day 3, day 8, day 14 day 28)
- cumulative incidence of the use of oxygen therapy, non-invasive ventilation or invasive ventilation ( composite criteria)(at day 14)
- Mortality(at day 14 and at day 28)