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
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Abstract
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 10 nasopharyngeal swab viral load by 0.5 log 10 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 10 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 )
Key Points
Question
Will early treatment of COVID-19 with a repurposed medication, camostat mesylate, improve clinical outcomes?
Findings
In this phase 2 randomized, double-blind placebo-controlled clinical trial that included 70 adults with early COVID-19, the oral administration of camostat mesylate treatment within 3 days of diagnosis prevented the loss of smell/taste and reduced the duration of illness.
Meaning
In the current COVID-19 pandemic, phase III testing of an inexpensive, repurposed drug for early COVID-19 is warranted.
Article activity feed
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SciScore for 10.1101/2022.01.28.22270035: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of this trial include the relative small sample size which make it difficult to drawn firm conclusions from any subgroup analysis such as age, gender, co-morbidities, etc. The results of this trial raises several key unanswered regarding …
SciScore for 10.1101/2022.01.28.22270035: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of this trial include the relative small sample size which make it difficult to drawn firm conclusions from any subgroup analysis such as age, gender, co-morbidities, etc. The results of this trial raises several key unanswered regarding camostat’s mechanism of action in improving the clinical course of COVID-19. First, while there was not a significant difference in viral load as determined by quantitative RT-PCR between camostat and placebo groups, we did not assess whether the viral load found represented infectious/viable virus. Camostat is predicted to inhibit viral entry2,4 so that it possible that the lack of difference in viral load in the two groups might be, at least in part, related to that mechanism. Because viremia is not a feature of COVID-19 and sampling sites other than the upper respiratoryy tract is not feasible in the outpatient clinical trial settting, it is difficult to assess systemic infection by viral load quantification. Second, camostat is a host-directed treatment aimed at inhibiting the cell-surface associated serine protease, TMPRSS2. It is likely that camostat has effects on other serine proteases, notably those found in the coagulation cascade as previously described 15,16. Given that the measurement of d-dimers is an important biomarker in COVID-19, it is possible that the salutary clinical effect of camostat may be on the host response at the level of endothelial cell-coagulation cascade interactions. Further work is needed to expl...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04353284 Completed Camostat Mesylate in COVID-19 Outpatients Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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