Clinical trial NCT04531748: Selective Estrogen Modulation and Melatonin in Early COVID-19
Official title: Selective Estrogen Modulation and Melatonin in Early COVID-19
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Covid19
Keywords: covid19
coronavirus
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2020-08-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak increase in COVID-19 Sign and Symptom score
timeFrame: Screening to 28 days
Secondary outcomes:
measure: Nadir Oxygen Saturation
timeFrame: Day 1 through day 14
measure: Peak Heart Rate
timeFrame: Day 1 through day 14
measure: Time to COVID-19 Sign and Symptom score resolution
timeFrame: Screening to 28 days
measure: Time to WHO 7-point ordinal scale score of 3 or higher
timeFrame: Day 1 to Day 30
Other outcomes:
Locations:
Study officials:
affiliation: The Cleveland Clinic
name: Reena Mehra, MD
role: PRINCIPAL_INVESTIGATOR
References: