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.
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.
Drug: Toremifene
Participants will be instructed to take 60mg of oral toremifene capsule daily, 30 minutes before bedtime.
Drug: Melatonin
Participants will be instructed to take the pills orally around the same time in the morning and 30 minutes prior to bedtime in the evening.
Other: Placebo
Oral placebo will be used with the same number and appearance to the pills as the interventions.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Reena Mehra, MD, Principal Investigator
The Cleveland Clinic