Camostat and Artemisia Annua vs Placebo in COVID-19 Outpatients

June 15, 2021 updated by: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Randomized, Double-blind, Placebo-controlled, Multicenter, Multi-arm, Phase II Trial of Novel Agents for the Treatment of Mild to Moderate COVID-19 Positive Outpatients

This is a randomized, double-blind, placebo-controlled, multi-arm, multicenter, phase II trial design to allow a rapid efficacy and toxicity assessment of potential therapies (camostat mesilate and artemisia annua) immediately after COVID-19 positive testing in mild to moderate disease and high-risk factors such as diabetes, hypertension, and obesity among others.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Coronavirus Disease 2019 (COVID-19) is a highly contagious disease, caused by a novel enveloped RNA beta-coronavirus, also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This disease has caused a global health crisis.

While the majority of patients with COVID-19 develop a mild or uncomplicated illness, approximately 20-30% of hospitalized patients have required intensive care support and 5% of those have multi-organ failure or shock. The case fatality rate ranges from 1 to 4% and it is higher among those with pre-existing comorbid conditions (high-risk) such as cardiovascular disease, diabetes mellitus, obesity, chronic respiratory disease, hypertension, and cancer.

To date, treatments for COVID-19 in high-risk individuals remain experimental and therapeutic strategies to deal with the infection are at best supportive, with prevention aimed at reducing transmission in the community as the best weapon. No proven therapies have been demonstrated to prevent progression of COVID-19 to severe illness in confirmed outpatients with COVID-19 and this is a critical unmet need for high-risk individuals and warrants study. Furthermore, there are no effective medications for the use in outpatients with confirmed mild to moderate COVID-19 disease.

This is a randomized, double-blind, placebo-controlled, multi-arm, multicenter, phase II trial design to allow a rapid efficacy and toxicity assessment of potential therapies, camostat mesilate (serine protease inhibitor) and Artemisia annua (unknown mechanism) immediately after COVID-19 positive testing in mild to moderate disease and high-risk factors such as diabetes, hypertension, and obesity among others. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus, such as Artemisia annua and camostat, will reduce the rate of a composite outcome of hospitalization due to COVID-19 pneumonia or the use of oxygen therapy; will be devoid of additional moderate to severe toxicities; and will improve viral clearance at Day 14 in high-risk individuals. The main hypothesis is that the clinical outcomes in COVID-19 infected patients at higher risk of poor outcomes following infection will be improved compared to the standard of care when introduced as an early intervention after diagnosis.

Study Type

Interventional

Enrollment (Actual)

246

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • None - Non-US/Canada
      • Mexico City, None - Non-US/Canada, Mexico, 14020
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥18 years
  • Laboratory-confirmed SARS-CoV-2 infection within 3 days (of proposed consent) or the presence of symptoms or signs providing a high probability of COVID-19 disease who have symptoms within 7 days prior to diagnosis as determined by Infectious Disease specialist or treating physicians.
  • Outpatients. No previous hospitalization within the past 3 months.

  • Subjects must have at least one of the following high-risk features for clinical deterioration:

    • Hypertension
    • Diabetes mellitus
    • Moderate to severe Chronic Obstructive Pulmonary Disease or asthma
    • Cancer patients who have received any immunosuppressive drugs within a year from enrollment.
    • Obesity as defined by a body mass index > 30 kg/m2.
    • Living in a nursing home or long-term facility
    • Underlying serious heart condition as determined by the treating physician
    • Immunocompromised subject as defined by the treating physician or by the Infectious Disease specialist
    • Ability to provide informed consent by the patient or healthcare proxy.
    • Ability to return for repeated testing and observation to the hospital.
    • Patients must have adequate organ and marrow function measured within the last 30 days as defined below:
  • platelets ≥100,000
  • aspartate transaminase or alanine transaminase ≤3 times institutional upper limit of normal
  • creatinine ≤ 1.5 times institutional upper limit of normal OR
  • glomerular filtration rate ≥45 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2

Exclusion Criteria:

  • Severe COVID-19 is defined by one or more of the following:

    • blood oxygen saturation ≤ 90%
    • partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300
    • lung infiltrates ≥ 50% within 24 to 48 hours

  • Life-threatening COVID-19 is defined as one or more of the following:

    • respiratory failure
    • septic shock
    • multiple organ dysfunction or failure
  • Weight less than 45 kg.
  • Pregnant or breast-feeding females
  • Subjects on dialysis or with creatinine clearance < 45 ml/min
  • Subjects who need antiviral administration due to severe viral diseases other than COVID-19, such as HIV, hepatitis B, and hepatitis C
  • Existing Division of Microbiology and Infectious Disease Toxicity Scale for determining the severity of adverse events grade 3 or greater.
  • Uncontrolled seizure disorder
  • Subjects with reflux esophagitis after chronic pancreatitis and gastrectomy surgery.
  • Patients with reflux esophagitis after surgery.
  • Known allergy to Artemisia annua or camostat mesilate.
  • Currently receiving any study medications for other indications.
  • Concurrent use of medication that would cause moderate or severe due to drug-drug interactions with study medication.

Specifically:

  • Patients receiving Artemisia annua tea may not be currently taking strong inducers of CYP2A6, including phenobarbital and rifampin.
  • Receipt in the 12 hours prior to enrollment, or planned administration during the 14-day study period that treating clinicians feel cannot be substituted for another medication, of any of the following: amiodarone; cimetidine; dofetilide; phenobarbital; phenytoin; or sotalol.
  • Cancer patients receiving active immunosuppressive treatment cannot be enrolled unless they are on a treatment holiday with no antineoplastic treatment with 3 weeks of enrollment.
  • Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
  • Subjects who have a history of drug and/or alcohol abuse within 52 weeks before screening
  • Enrollment on other experimental therapies for COVID-19.
  • Inability to receive enteral medications
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements.
  • Subjects who have a history of drug and/or alcohol abuse within 52 weeks before screening
  • Any other condition that in the opinion of the treating physician justifies exclusion from the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Camostat mesilate
100 mg tablet, 600 mg/day. Oral, 2 tablets three times a day, after a meal (600 mg total daily dose) Days 1-14.
Drug: Camostat Mesilate
Tablets
Other Names:
  • Camostat
Placebo Comparator: Camostat Placebo
Matched placebo
Drug: Camostat Mesilate
Tablets
Other Names:
  • Camostat
Active Comparator: Artemisia annua
Tea 225mg per bag,1350 mg/day. Oral, one 8 oz brewed tea (two bags) three times a day, Days 1-14.
Drug: Artemisia Annua Leaf
Tea bags
Other Names:
  • Artemisia annua
  • Artemisia
Placebo Comparator: Artemisia annua Placebo
Matched placebo
Drug: Artemisia Annua Leaf
Tea bags
Other Names:
  • Artemisia annua
  • Artemisia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of hospitalizations and oxygen use
Time Frame: 14 days
Decrease in a composite outcome of hospitalization and supplemental oxygen use at day 14 between treatment pairs.
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Investigators

  • Principal Investigator: Jose G Gotes Palazuelos, MD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2020

Primary Completion (Actual)

June 10, 2021

Study Completion (Actual)

June 10, 2021

Study Registration Dates

First Submitted

August 26, 2020

First Submitted That Met QC Criteria

August 26, 2020

First Posted (Actual)

August 28, 2020

Study Record Updates

Last Update Posted (Actual)

June 21, 2021

Last Update Submitted That Met QC Criteria

June 15, 2021

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3421

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

All IPD results in the publication

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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