Selective Estrogen Modulation and Melatonin in Early COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Peak increase in COVID-19 Sign and Symptom score
研究概览
简要总结
This study is a randomized, double-blind, controlled clinical trial to evaluate the effects of toremifene and/or melatonin in adults with mild COVID-19.
详细描述
This study is a randomized, double-blind, controlled clinical trial to evaluate the effects of a 14 day intervention of toremifene plus melatonin or melatonin in adults with mild COVID-19.
The study will evaluate the progression of clinical signs and symptoms (fever, dyspnea, cough, fatigue daily score) and any adverse outcomes in comparison to placebo for 30 days.
The successful completion of this project offers high potential to identify effective treatment (e.g., toremifene plus melatonin and/or melatonin) rapidly for patients with early COVID-19 and to provide, important, fundamental mechanistic insights.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The Medical Safety Officer will not be blinded.
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
- •Clinical testing positive for SARS-Cov-2 by standard RT-PCR or equivalent test
- •Willing and able to give informed consent for participation in the study and agrees with the study and its conduct
- •Age>18 years
- •Fluency in English or Spanish language, functional literacy
- •Able to swallow pills
- •COVID-19 Daily Sign and Symptom score of 2-8
排除标准
- •History of deep venous thrombosis or pulmonary embolism
- •Hypercoagulable disorders (e.g. lupus anticoagulant, deficiency of protein C or S)
- •Embolic stroke
- •Liver disease
- •History of endometrial cancer
- •Menopausal hormone therapy or oral, injectable or transdermal contraceptives
- •Depression which is not optimally treated (assessed via medical record and patient will be asked if she/he feels that depression is optimally treated)
- •Medications which prolong the QT interval (e.g. hydroxychloroquine or azithromycin) or those with long QT syndrome (heritable or acquired). Examples of other medications which prolong the QT interval include: Agents generally accepted to prolong QT interval include Class 1A (e.g., quinidine, procainamide, disopyramide) and Class III (e.g., amiodarone, sotalol, ibutilide, dofetilide) antiarrhythmics; certain antipsychotics (e.g., thioridazine, haloperidol); certain antidepressants (e.g., venlafaxine, amitriptyline); certain antibiotics (e.g., erythromycin, clarithromycin, levofloxacin, ofloxacin); and certain anti-emetics (e.g., ondansetron, granisetron) (Please refer to Appendix for detailed list of medications)
- •Inability to participate in follow up assessment
- •Dementia/cognitive dysfunction
- •Pregnancy (pregnancy testing will be performed to determine eligibility)
- •Breastfeeding
- •Participating in other COVID-19 trials
- •Immunodeficiency (including HIV, Hepatitis C, bone marrow transplant history, on immunosuppressant medications)
- •Current hospitalization
- •Seizure disorder
- •History of rheumatoid arthritis
- •Heart failure (NYHA Class III or IV)
- •Current diagnosis of renal insufficiency/failure
- •QTc >470ms per 12-lead ECG
- •Calcium >10.2mg/dL
- •AST or ALT > 2x upper limit of normal (ULN)
- •D-dimer >= 1000 u/L
- •Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2
- •On other treatment(s) for COVID-19 (e.g. hydroxychloroquine, remdesivir)
- •Anticoagulant medications (e.g. coumadin, glycoprotein IIa/IIIb inhibitors)
- •Clinical signs of severe or critical severity of COVID-19 (e.g. shortness of breath at rest, Respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air)
- •Use of supplemental oxygen
- •Moderate to severe pulmonary disease up to PI discretion
研究组 & 干预措施
Toremifene + Melatonin
100mg oral Melatonin on Days 1 & 2 (40mg in the morning and 60mg in the evening), 60 mg on Days 3-14, (20mg in the morning and 40mg in the evening).
60mg oral toremifene daily days 1-14.
干预措施: Toremifene (Drug)
Toremifene + Melatonin
100mg oral Melatonin on Days 1 & 2 (40mg in the morning and 60mg in the evening), 60 mg on Days 3-14, (20mg in the morning and 40mg in the evening).
60mg oral toremifene daily days 1-14.
干预措施: Melatonin (Drug)
Melatonin + Placebo
100mg oral Melatonin on Days 1 & 2 (40mg in the morning and 60mg in the evening) and 60 mg on Days 3-14, (20mg in the morning and 40mg in the evening).
干预措施: Melatonin (Drug)
Melatonin + Placebo
100mg oral Melatonin on Days 1 & 2 (40mg in the morning and 60mg in the evening) and 60 mg on Days 3-14, (20mg in the morning and 40mg in the evening).
干预措施: Placebo (Other)
Placebo
Oral placebo will be used with the same number and appearance to the pills as the interventions
干预措施: Placebo (Other)
结局指标
主要结局
Peak increase in COVID-19 Sign and Symptom score
时间窗: Screening to 28 days
Score total of 0-12 assessed daily. Each category based on severity of symptoms of Cough, Shortness of breath, Fatigue/tiredness and daily temperature on a rating scale of 0-3.
次要结局
- Nadir Oxygen Saturation(Day 1 through day 14)
- Peak Heart Rate(Day 1 through day 14)
- Time to COVID-19 Sign and Symptom score resolution(Screening to 28 days)
- Time to WHO 7-point ordinal scale score of 3 or higher(Day 1 to Day 30)
研究者
Reena Mehra, MD
Director, Sleep Disorders Research, Neurological Institute
The Cleveland Clinic