Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19

Study Overview
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Brief Summary
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The overall objective of this study is to evaluate the clinical efficacy of oral famotidine in symptomatic non-hospitalized patients with confirmed COVID-19. This study is expected to enroll up to 84 patients with mild to moderate symptoms divided into each of the two study arms. Clinical outcomes of the two treatment arms will be compared. This study will be conducted virtually/remotely.

Detailed Description
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The outbreak of coronavirus disease 2019 (COVID 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was first reported in Wuhan, China, in 31 December 2019 and was declared as a global health emergency on 30 January 2020. Currently, there are no definitive vaccine, therapeutic antibody, or antiviral drug countermeasures currently authorized by the FDA for prevention or treatment of mild to moderate COVID-19 disease. Famotidine is a histamine-2 receptor antagonist, widely available over-the-counter and at low cost, does not interact with other medications and is safely used for suppression of gastric acid production. This makes it a candidate medication for an ambulatory setting to alleviate the symptoms and shorten the symptomatic period in this population. In a case series of 10 patients with COVID-19 who self-medicated with oral famotidine, significant improvement of symptoms was associated with famotidine use after 24-48 hours. These effects were noted in patients who mostly took doses of 80mg three times daily suggesting that famotidine's action is either through its main known high affinity target, the histamine type 2 receptor or through combined inhibition of histamine receptors. Famotidine may work through reduction of H2R signaling on monocytes with a resulting reduction of cytokine release. The working hypothesis is that famotidine will be superior to placebo in reducing disease related symptoms in non-hospitalized COVID-19 patients with mild or moderate disease. Patients will be monitored for the duration of the study, as well as be asked to record the severity of their symptoms through a daily questionnaire. Current standard of care (SOC) for patients with mild to moderate COVID-19 in the outpatient setting is to assess risk for severe disease and determine the need for an in-person visit, thromboprophylaxis and adjustment of home medication regimen. If the SOC for COVID-19 patients in the outpatient setting changes during the course of the study, a request will be submitted to modify sections of the protocol.

Official Title
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A Randomized, Double-Blind, Comparative Trial of the Safety and Efficacy of Famotidine vs Placebo for the Treatment of Non-Hospitalized Symptomatic Adults With COVID-19

Conditions
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Covid-19

Intervention / Treatment
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* Drug: Famotidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. Understands and agrees to comply with planned study procedures. Adult ≥18 years of age at time of enrollment. Subject consents to randomization. Subject has confirmed COVID-19 disease < 72 hours prior to randomization. Subject has been experiencing symptoms for >1 day but ≤7 days. Able to use an electronic tablet and Bluetooth devices. Subject has mild to moderate COVID-19 which is defined as (equivalent to 1, 2 on the WHO scale): Patient does not require immediate admission to the hospital within 24 hrs of initial assessment Patient does not require supplemental oxygen due to COVID-19 Patient has a score of 2 (moderate) in at least 3 of the symptoms in the COVID- 19 symptom score Exclusion Criteria: Any exposure to investigational medications targeting COVID-19 during the present disease. These include recently approves antibodies (passive immunization) for treatment of COVID-19. Use of famotidine within the last 30 days for any indication, e.g. medicating gastric ulcer or recent off label use for COVID-19. Severe COVID-19 disease at time of enrollment requiring admission to hospital. History of Stage 3 severe chronic kidney disease, i.e. eGFR of < 60ml/min. Allergy to famotidine or non-medical ingredients of the study tablet. Known to be immunocompromised by treatment for existing disease due to the immunomodulatory effects of famotidine and therefore possible effects on the pre- existing disease or the immunosuppressive therapy. Patients currently using tizanidine. Documented deficiency of any of the following minerals: Al, Cu, Mn, Fe and Zn. Inability to perform the tasks required for the patient reported outcome measure recordings, including but not restricted to limited language proficiency. Have symptoms of dysphagia or inability to swallow size #000 capsules.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-Blind Comparative Placebo Controlled Trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Famotidine<br>Participants in this study arm will receive standard of care and prescribed famotidine at 80mg TID for a maximum of 14 days, or until hospital admission. | Drug: Famotidine<br>* Standard or care treatment plus prescribed famotidine<br>|
| Placebo Comparator: Placebo<br>Participants in this study arm will receive standard of care and placebo for a maximum of 14 days. | Drug: Placebo<br>* Standard of care treatment plus placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of symptom resolution | Measured by the cumulative incidence of symptom resolution using the COVID-19 Symptom Score derived from the answers to a questionnaire based on the NIH endorsed guidelines and the recent FDA guidelines for studying COVID-19 in an outpatient setting. A shorter version has been utilized as a scoring system in the case series of famotidine use in non-hospitalized patients with COVID-19. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of symptom resolution | Assessed by modelling the resolution of cumulative symptoms over time | Day 28 | 
| Cumulative incidence of symptom resolution | Assessed using the COVID-19 Symptom Score | Day 60 | 
| Relative change of symptoms | Assessed using the COVID-19 Symptom Score | Day 7 | 
| Assessment of Serious Adverse Events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | Day 60 | 
| Clinical improvement | Assessed using the 9-point ordinal scale recommended by the WHO for trials enrolling patients with COVID-19. | Day 28 | 
| Improvement in peripheral oxygen saturation | Measured by pulse oximetry in % oxygen saturation. | Day 7 | 
| Mortality | Assessed by counting mortality in each arm | Day 28 | 
| Comparative proportions of hospitalized patients | Measured by the proportions of patients having been hospitalized by Day 28. | Day 0-28 | 
| Change in CRP | Measured by CRP [mg/L] | Day 7, 14, and 28. | 
| Change in procalcitonin | procalcitonin [microg/L] | Day 7, 14, and 28. | 
| Change in ferritin | ferritin [microg/L] | Day 7, 14, and 28. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, Coronavirus, Famotidine, Outpatient, Non-Hospitalized