Covid-19 living Data

Camostat Mesilate vs Placebo (RCT)

Mild outpatients

FOREST PLOTS -2023-01-27

Studies description

Trial NCT04353284
Publication Chupp G, medRxiv (2022) (preprint)
Dates: 2020-06-01 to 2021-04-30
Funding: Mixed (Kenneth C. Griffin; the Prostate Cancer Foundation; the COVID-19 Early Treatment Fund; the Harrington Discovery Institute; institutional funds from the Department of Internal Medicine at the Yale School of Medicine, and the Yale Center for Clinical Investigation; the United State Public Health Service; Ono Pharmaceuticals provided the study drug.)
Conflict of interest: No

Trial NCT04518410
Publication ACTIV-2 - Jilg N, Top Antivir Med (2022) (unpublished results)

Funding: Not reported/unclear
Conflict of interest: *

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / USA Follow-up duration (days): 28
Inclusion criteria	Hospitalized adults with mild-moderate COVID-19
Exclusion criteria	NR
Interventions
	Treatment Camostat Mesilate 200 mg orally every 6 hours for 7 days
	Control Placebo
Participants
	Randomized NR Analyzed 215 participants Placebo=107 Camostat Mesilate=108
	Characteristics of participants N= 215 Mean age : NR 0 males Severity : Mild: n= / Asymptomatic: n=
Primary outcome
	In the register 1) COVID-19 symptom duration (Phase 2) [ Time Frame: Up to Day 28 ] Duration defined as the number of days from start of investigational agent to the first of two consecutive days when any symptoms scored as moderate or severe as study entry (pre-treatment) are scored as mild or absent; and any symptoms scored as mild or absent at study entry are scored as absent, AND any symptoms scored as mile or absent at study entry (pre-treatment) are scored as absent. Targeted symptoms are: Feeling feverish; cough, shortness of breath or difficulty breathing; sore throat; body pain or muscle pain/aches; fatigue (low energy); headache, chills, nasal obstruction or congestion (stuffy nose); nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3) 2) Quantification of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Day 3 ] Measured as quantification (4) Quantification of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Day 14 ] Measured as quantification (5) Proportion of participants with new adverse event (AE) ≥ Grade 3 (Phase 2) [ Time Frame: Thru Day 28 ] Cumulative incidence of death due to any cause or hospitalization due to any cause (Phase 3) [ Time Frame: Thru Day 28 ] Hospitalization defined as ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19
	In the report Safety and efficacy of camostat to reduce the duration of COVID-19 symptoms and increase the proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal (NP) swabs on days 3, 7, and 14
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	*
General comment	The published abstract and study registry were used in data extraction. No review specific outcomes were extractable. This study is part of the the ACTIV-2 platform trial.

Trial NCT04583592
Publication CAMELOT - Jilg N, Top Antivir Med (2022) (results posted on registry)

Funding: Not reported/unclear
Conflict of interest: *

Methods
	RCT Blinding: quadruple blinding
	Location : Multicenter / USA Follow-up duration (days): 28
Inclusion criteria	Adults willing and able to provide informed consent before performing study procedures Adults ≥18 years of age at time of informed consent Participants must have written notification of laboratory confirmed COVID-19 infection performed prior to screening, at a local laboratory by RT-PCR or other commercial or public health assay in any specimen and participants must be randomized within 72 hours of receiving the above notification of laboratory confirmed COVID-19 Have a mild or moderate form of COVID-19 defined as SpO2 > 94% at screening Participants must have at least 1 of the following risk factors for severe illness Aged 65 years or older, Hypertension, Diabetes mellitus, Chronic lung disease including asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease (eg, idiopathic pulmonary fibrosis) Chronic cardiac conditions, including coronary artery disease (CAD), heart failure, congenital heart disease, cardiomyopathy, Severe obesity (body mass index [BMI] ≥ 40 kg/m^2), Chronic liver disease, including cirrhosis Must agree not to enroll in another study of an investigational agent or take any other drug that has been granted Emergency Use Authorization prior to completion of Day 28 If women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for 90 days after receiving the last dose of study drug
Exclusion criteria	Physician makes a decision that trial involvement is not in participants' best interest, or has any condition that does not allow the protocol to be followed safely Known severe liver disease (eg, Child Pugh score > 12, AST >5 times upper limit) SaO2/SPO2 ≤94% on room air condition, or the Pa02/Fi02 ratio < 300 mgHg Known allergic reaction to camostat mesilate or one of its excipients Known severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m^2) or receiving dialysis Pregnant or breastfeeding, or positive pregnancy test in a predose examination Receipt of any experimental treatment for COVID-19, including agents with demonstrated or possible direct acting antiviral activity, including, but not limited to, remdesivir, hydroxychloroquine, lopinavir/ritonavir, tocilizumab, or ivermectin, within the 30 days prior to the time of the screening evaluation. No off label use of a drug for COVID 19 is allowed History of human immunodeficiency virus infection on highly active antiretroviral therapy (HAART)
Interventions
	Treatment Camostat Mesilate 200 mg orally 4 times a day for 14 days
	Control Placebo
Participants
	Randomized participants : Placebo=101 Camostat Mesilate=194
	Characteristics of participants N= 295 Mean age : NR 126 males Severity : Mild: n= 295/ Asymptomatic: n=*
Primary outcome
	In the register Disease Progression at Day 28 [ Time Frame: 28 days ] Disease progression will be defined as the number of participants requiring hospitalization (including emergency room visit) or who die due to any cause within 28 days of randomization.
	In the report Hospitalization or death within 28 days
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Low
General comment	This is an unpublished trial whose results have been reported in ClinicalTrials.gov. The trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The trial was registered prospectively and no important changes were made to primary or secondary outcomes after recruitment start. The trial (n=295) achieved its target sample size (n=300). This study was updated on January 26th, 2023 with data extracted from the published abstract.

Trial NCT04524663
Publication COPS-2003 - NCT04524663, Unpublished (2022) (results posted on registry)

Funding: Not reported/unclear
Conflict of interest: *

Methods
	RCT Blinding: double blinding
	Location : Single center / USA Follow-up duration (days): 28
Inclusion criteria	Diagnosis of COVID-19 disease as presence of mild-moderate symptoms without signs of respiratory distress, with FDA-cleared molecular diagnostic assay positive for SARS-CoV-2 within 72 hours prior to informed consent Males must be sterile, OR agree not to donate semen AND agree to strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication Females must be unable to bear children, OR ensure that their male partner is incapable of fathering a child, OR, if of childbearing potential will strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication Females must agree to stop breast-feeding prior to first dose of study drug and through seven days after completing therapy Females must have a negative pregnancy test at screening Participant agrees to maintain home or other quarantine as recommended by the study physician, except to visit the study site as required by the protocol
Exclusion criteria	Concomitant bacterial respiratory infection documented by respiratory culture. NOTE: Subjects on empirical antibiotic treatment for possible but unproven bacterial pneumonia, but who are positive for SARS-CoV-2, are allowed in the study Previous use of antiviral drugs that may be active against Covid-19 Abnormal laboratory test results at screening Use of adrenocorticosteroids (except topical or inhaled preparations or oral preparations equivalent to or less than 10 mg of oral prednisone) or immunosuppressive or immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers). NOTE: Treatment of study participants following institutional COVID-19 treatment policies or guidelines, including the use of immunomodulatory medications, is permitted. This excludes treatment with agents that have the potential for direct antiviral activity, including convalescent plasma and NO, and co-enrollment into other clinical studies that evaluate investigational agents for COVID-19 Serious chronic disease (e.g., human immunodeficiency virus [HIV], cancer requiring chemotherapy within the preceding 6 months, and/or moderate or severe hepatic insufficiency) Previously received camostat mesilate within the past 30 days Advanced kidney disease Advanced liver disease History of alcohol or drug abuse in the previous 6 months Psychiatric illness that is not well controlled (defined as stable on a regimen for more than one year) Taken another investigational drug within the past 30 days Seemed by the Investigator to be ineligible for any reason
Interventions
	Treatment Camostat Mesilate 200 mg orally 4 times per day for 10 days
	Control Placebo
Participants
	Randomized participants : Camostat Mesilate=25 Placebo=24
	Characteristics of participants N= 49 Mean age : NR 32 males Severity : Mild: n= 49/ Asymptomatic: n=*
Primary outcome
	In the register Area Under the Curve (AUC) of Shedding of SARS-CoV-2 Virus [ Time Frame: Days 1-10 ]
	In the report NR
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	This is an unpublished trial whose results have been reported in ClinicalTrials.gov. The trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The trial was registered prospectively and no important changes were made to primary or secondary outcomes after recruitment start.

Trial NCT04625114
Publication Tobback E, Int J Infect Dis (2022) (published paper)
Dates: 2020-11-04 to 2021-06-30
Funding: Mixed (Ono Pharmaceuticals Co. Ltd. (Osaka, Japan) provided the study drug, camostat mesylate. Byteflies (Antwerp, Belgium) provided telemonitoring devices and technological support. No further funding was received.)
Conflict of interest: No

Methods
	RCT Blinding: double blinding
	Location : Single center / Belgium Follow-up duration (days): 28
Inclusion criteria	Symptomatic (maximum 5 days) and asymptomatic patients confirmed COVID-19 infection by a reverse transcription-polymerase chain reaction (RT-PCR) 18 years or older willing to follow the study interventions, and capable of understanding and signing the informed consent form Women of childbearing potential or men of reproductive potential had to be willing to use contraception during and until the end of the study.
Exclusion criteria	The need for or being at high risk of hospitalization pregnancy as checked by a urine pregnancy test at baseline or breastfeeding severe chronic pancreatitis postoperative reflux esophagitis.
Interventions
	Treatment Camostat Mesilate 300 mg orally three times a day for 5 days, with possible extension to 10 days
	Control Placebo
Participants
	Randomized participants : Camostat Mesilate=66 Placebo=30
	Characteristics of participants N= 96 Mean age : NR 41 males Severity : Mild: n= 77/ Asymptomatic: n=13
Primary outcome
	In the register Efficacy in terms of viral load or surrogate [ Time Frame: 5 days ] The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) log10 viral load. Surrogate market CT value will be used as well.
	In the report Change in the shedding of the SARS-CoV-2 virus as measured by Ct obtained from nasopharyngeal swabs on days 1 and 5.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The primary outcome in the article reflects that in the registry. The trial did not achieve its target sample size due to a lack of available enrollees and the per protocol decision was taken to conduct this interim analysis, after which recruitment was stopped.