A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste.

IMPORTANCE

Early treatment of mild SARS-CoV-2 infection might lower the risk of clinical deterioration in COVID-19.

OBJECTIVE

To determine whether oral camostat mesylate would reduce upper respiratory SARS-CoV-2 viral load in newly diagnosed outpatients with mild COVID-19, and would lead to improvement in COVID-19 symptoms.

DESIGN

From June, 2020 to April, 2021, we conducted a randomized, double-blind, placebo-controlled phase 2 trial.

SETTING

Single site, academic medical center, outpatient setting in Connecticut, USA.

PARTICIPANTS

Of 568 COVID-19 positive potential adult participants diagnosed within 3 days of study entry and assessed for eligibility, 70 were randomized and 498 were excluded (198 did not meet eligibility criteria, 37 were not interested, 265 were excluded for unknown or other reasons). The primary inclusion criteria were a positive SARS-CoV-2 nucleic acid amplification result in adults within 3 days of screening regardless of COVID-19 symptoms.

INTERVENTION

Treatment was 7 days of oral camostat mesylate, 200 mg po four times a day, or placebo.

MAIN OUTCOMES AND MEASURES

The primary outcome was reduction of 4-day log nasopharyngeal swab viral load by 0.5 log compared to placebo. The main prespecified secondary outcome was reduction in symptom scores as measured by a quantitative Likert scale instrument, Flu-PRO-Plus modified to measure changes in smell/taste measured using FLU-PRO-Plus.

RESULTS

Participants receiving camostat had statistically significant lower quantitative symptom scores (FLU-Pro-Plus) at day 6, accelerated overall symptom resolution and notably improved taste/smell, and fatigue beginning at onset of intervention in the camostat mesylate group compared to placebo. Intention-to-treat analysis demonstrated that camostat mesylate was not associated with a reduction in 4-day log NP viral load compared to placebo.

CONCLUSIONS AND RELEVANCE

The camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell. Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load. Additional clinical trials are warranted to validate the role of camostat mesylate on SARS-CoV-2 infection in the treatment of mild COVID-19.

TRIAL REGISTRATION

Clinicaltrials.gov, NCT04353284 (04/20/20)(https://clinicaltrials.gov/ct2/show/NCT04353284?term=camostat+%2C+yale&draw=2&rank=1).