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Camostat and Artemisia Annua vs Placebo in COVID-19 Outpatients

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ClinicalTrials.gov Identifier: NCT04530617
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : October 22, 2020
Sponsor:
Collaborators:
Instituto Nacional de Cardiologia Ignacio Chavez
Hospital General de Mexico
Hospital General Dr. Manuel Gea González
Information provided by (Responsible Party):
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Tracking Information
First Submitted Date  ICMJE August 26, 2020
First Posted Date  ICMJE August 28, 2020
Last Update Posted Date October 22, 2020
Actual Study Start Date  ICMJE October 5, 2020
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Camostat and Artemisia Annua vs Placebo in COVID-19 Outpatients
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
A randomized, placebo-controlled, parallel, multicenter, multi-arm, phase II trial of novel agents for treatment of high-risk COVID-19 positive outpatients. Subjects who meet the inclusion/exclusion criteria and have properly signed the informed consent will be randomized to the test group or placebo group in the ratio of 1:1:1:1.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
The masking of the protocol will be maintained throughout the duration of the study. This will be done with the use of a matched placebo and a non-continuous coding (tablets in the case of camostat and tea bags/coffer for Artemisia) that has the same description and dose as the interventions so that both, the investigators and the patient does not know the treatment assignment.
Primary Purpose: Treatment
Condition  ICMJE
  • Covid19
  • Diabetes
  • Hypertension
  • Obesity
Intervention  ICMJE
  • Drug: Camostat Mesilate
    Tablets
    Other Name: Camostat
  • Drug: Artemisia Annua Leaf
    Tea bags
    Other Names:
    • Artemisia annua
    • Artemisia
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Camostat Mesilate
  • Placebo Comparator: Camostat Placebo
    Matched placebo
    Intervention: Drug: Camostat Mesilate
  • 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.
    Intervention: Drug: Artemisia Annua Leaf
  • Placebo Comparator: Artemisia annua Placebo
    Matched placebo
    Intervention: Drug: Artemisia Annua Leaf
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 26, 2020)
360
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jose G Gotes Palazuelos, MD +525554870900 ext 8337 jose.gotesp@incmnsz.mx
Contact: David Kershenobich Stalnikowitz, MD +525554870900 ext 6109 kesdhipa@yahoo.com
Listed Location Countries  ICMJE Mexico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04530617
Other Study ID Numbers  ICMJE 3421
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: All IPD results in the publication
Responsible Party Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Sponsor  ICMJE Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators  ICMJE
  • Instituto Nacional de Cardiologia Ignacio Chavez
  • Hospital General de Mexico
  • Hospital General Dr. Manuel Gea González
Investigators  ICMJE
Principal Investigator: Jose G Gotes Palazuelos, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
PRS Account Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP