Phase 2 Clinical Trial Shows That Famotidine Is Effective In Treating COVID-19

The study findings of a phase 2 clinical trial led by Feinstein Institutes for Medical Research-New York and Cold Spring Harbor Laboratory shows that the common heart burn drug Famotidine is effective in treating COVID-19 disease especially for those with in mild to moderate cases.

The study findings were published in the peer reviewed journal: BMJ Gut
https://gut.bmj.com/content/early/2022/02/09/gutjnl-2022-326952

The search for safe, effective and affordable treatments for COVID-19 remains a global health priority. COVID-19 is pandemic, with an estimated 319 M cases and 5.5 M deaths worldwide to date.1 Restrictive public health measures in response to COVID-19 have led to unprecedented negative impacts on society.2

COVID-19 is caused by the SARS-CoV-2.3 On body entry, SARS-CoV-2 docks to the widely expressed ACE24 5 and is internalised into the cell.6 7 Viral replication causes cell death and engages the immune system.8

Toll-like receptor 3 (TLR3) binds viral double-stranded RNA, leading to nuclear factor kappa-light-chain-enhancer of activated B cells directed transcriptional activation of type-I interferon and cytokine production.9 10

In most cases, the resulting inflammation and activation of the adaptive immune system leads to viral clearance, early resolution of inflammation and acquired immunity after a mild or even asymptomatic disease period.11

A significant minority of patients, however, experience moderate or severe COVID-19 caused by either suboptimal immune activation or non-abrogated inflammatory and immune overactivation, commonly referred to as a ‘cytokine storm’.10 This may explain why factors that predispose a patient to inflammation12 are risk factors for a poor outcome from COVID-19.13

COVID-19 preventions and treatments can be classified into the categories vaccination, anti-viral medication and host response modulator. Vaccinations prime the immune system, reduce disease severity and mortality and prevent spread of the disease.14 15 Unfortunately, their effectiveness may be compromised by viral variants, such as Delta or Omicron.16 17

Vaccine uptake is limited by non-concordance, cost, and supply and distribution hurdles.18 Similar factors may diminish the global impact of emerging anti-viral medications that have recently shown promising results in reducing hospitalisation and death of patients with risk factors for poor outcome.19–21

The sustained host inflammatory response has been modulated using anti-inflammatory medications and immune suppressants in hospitalised patients. For example, dexamethasone reduced mortality in hospitalised, oxygen-dependent patients with COVID-19.22

It has been shown to modulate interferon programming in patients with severe COVID-19.23 In outpatients with COVID-19, the selective serotonin reuptake inhibitor fluvoxamine reduced hospitalisation, but no mechanism is known.24

Famotidine is a widely available, safe, low-cost candidate medication for COVID-19. This selective histamine H2-receptor (H2R) antagonist reduced type-I interferon release from SARS-CoV-2-infected epithelial cells in a TLR3-dependent manner.9

Famotidine intake as an antacid has been associated with improved clinical outcome in several retrospective cohort studies of hospitalised patients,25 26 but some studies found no effect or negative associations.27

In a case series of unvaccinated outpatients with moderate COVID-19, oral famotidine at 80 mg three times a day was well tolerated and associated with rapid symptomatic and physiological improvement.28

Famotidine, as a result, has been frequently prescribed to non-hospitalised patients with COVID-19, without clinical trial data supporting biological or clinical efficacy.

We performed a randomised, double-blind, placebo-controlled, phase 2 clinical trial of oral famotidine (80 mg three times a day) and deeply profiled the enrolled diverse, non-hospitalised patients with mild to moderate symptoms from COVID-19.

We devised a fully remote clinical trial strategy to reduce patient burden and exposure of the public and healthcare personnel. We aimed to assess the benefit of famotidine on resolution of symptoms and inflammation in patients with COVID-19.