Back to resultsA Study of Combination Therapies to Treat COVID-19 Infection
Primary Purpose
COVID, COVID-19, Corona Virus Infection
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
hydroxychloroquine
Azithromycin
Ritonavir
Lopinavir
Sponsored by
About this trial
This is an interventional treatment trial for COVID
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent, demonstrating that the subject understands the procedures required for the study and the purpose of the study
- Healthy, ambulant male or female subjects 18 years of age to 65 years of age
- Positive test for COVID-19 by RT-PCR at screening
- Subjects must agree to practice at least one highly effective method of birth control for the duration of the study. This includes condoms with spermicide, oral birth control pills, contraceptive implants, intra-uterine devices, or diaphragms. Subjects not of reproductive potential will be exempt (e.g. post-menopausal, surgically sterilized)
- Subjects must agree they will do their best to attend the treatment facility daily for 10 days
Exclusion Criteria:
- Refusal to sign informed consent form
- Negative test for COVID-19 by RT-PCR at screening
- Severe disease symptomatically including pneumonia, respiratory distress, tachypnea, shortness of breath, temperature > 38 degrees; pleuritic pain, or frequent cough.
- Known drug allergy to any of the investigational medications
- Currently taking medication with known drug interactions with investigational medications (listed in appendix)
- Prescription or other antiviral medications
- Any comorbidities which constitute health risk for the subject
- Pregnant or lactating females;
- weight < 110lb;
- porphyria
- established retinal disease
- Inability to attend daily for 10 days
Any contraindications for treatment with hydroxychloroquine
- Hypoglycemia
- Known G6PD deficiency
- Porphyria
- Anemia
- Neutropenia
- Alcoholism
- Myasthenia gravis
- Skeletal muscle disorders
- Maculopathy
- Changes in visual field
- Liver disease
- Psoriasis
- History of QT >500msec
- History of torsades de pointes
- Anemia from pyruvate kinase and G6PD deficiencies
- Abnormal EKG with QT prolongation acquired or from birth
- History of jaundice or high fevers prior to developing COVID-19
- Treatment with any of the medications listed in Appendix II
- Treatment with any anti-epileptic medication
- Treatment with any other drug not listed that affects the QT interval
Sites / Locations
- ProgenaBiome
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dual Therapy
Quadruple Therapy
Arm Description
Dual Therapy utilizing hydroxychloroquine and azithromycin.
Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin
Outcomes
Primary Outcome Measures
Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores
Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
Efficacy of Treatment by Time to Non-Infectivity
Time to non-infectivity as measured by PCR testing
Secondary Outcome Measures
Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores
Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores.
Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
Safety of Dual Therapy as Measured by Complete Blood Count
Changes in blood parameters measured in a Complete Blood Count (CBC).
Safety of Quadruple Therapy as Measured by Complete Blood Count
Changes in blood parameters measured in a Complete Metabolic Panel.
Safety of Dual Therapy as Measured by Metabolic Panel -Albumin
Changes in serum albumin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin
Changes in serum albumin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio
Changes in serum albumin/globulin ratio
Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio
Changes in serum albumin/globulin ratio
Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase
Changes in serum alkaline phosphatase levels
Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase
Changes in serum alkaline phosphatase levels
Safety of Dual Therapy as Measured by Metabolic Panel - AST
Changes in serum AST levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - AST
Changes in serum AST levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT
Changes in serum ALT levels
Safety of Dual Therapy as Measured by Metabolic Panel ALT
Changes in serum ALT levels
Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio
Changes in serum BUN/Creatinine Ratio
Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio
Changes in serum BUN/Creatinine Ratio
Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN
Changes in serum Blood Urea Nitrogen levels
Safety of Dual Therapy as Measured by Metabolic Panel - BUN
Changes in serum Blood Urea Nitrogen levels
Safety of Dual Therapy as Measured by Metabolic Panel - Calcium
Changes in serum calcium levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium
Changes in serum calcium levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide
Changes in serum carbon dioxide levels
Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide
Changes in serum carbon dioxide levels
Safety of Dual Therapy as Measured by Metabolic Panel - Chloride
Changes in serum chloride levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride
Changes in serum chloride levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine
Changes in serum creatinine levels
Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine
Changes in serum creatinine levels
Safety of Dual Therapy as Measured by Metabolic Panel - Globulin
Changes in serum globulin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin
Changes in serum globulin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose
Changes in blood glucose levels
Safety of Dual Therapy as Measured by Metabolic Panel - Glucose
Changes in blood glucose levels
Safety of Dual Therapy as Measured by Metabolic Panel - Potassium
Changes in blood potassium levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium
Changes in blood potassium levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin
Changes in serum total bilirubin levels
Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin
Changes in serum total bilirubin levels
Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein
Changes in serum total protein levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein
Changes in serum total protein levels
Safety of Dual Therapy as Measured by Treatment Related SAE
Presence or absence of treatment related serious adverse events Grade III or higher
Safety of Quadruple Therapy as Measured by Treatment Related SAE
Presence or absence of treatment related serious adverse events Grade III or higher
Full Information
NCT ID
NCT04459702
First Posted
June 25, 2020
Last Updated
April 6, 2021
Sponsor
ProgenaBiome
Collaborators
Big Corona Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04459702
Brief Title
A Study of Combination Therapies to Treat COVID-19 Infection
Official Title
A Phase IIa Randomized, Controlled Study of Combination Therapies to Treat COVID-19 Infection
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Was never started
Study Start Date
July 2020 (Anticipated)
Primary Completion Date
July 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ProgenaBiome
Collaborators
Big Corona Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study seeks to determine whether dual or quadruple therapy is more effective in treating COVID-19.
Detailed Description
In this study, patients will be administered either dual or quadruple therapy and have PCR tests run daily to determine efficacy as indicated by time to non-infectivity
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID, COVID-19, Corona Virus Infection, Coronavirus Infection, Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere, Coronavirus-19, SARS-CoV 2, SARS Pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dual Therapy
Arm Type
Experimental
Arm Description
Dual Therapy utilizing hydroxychloroquine and azithromycin.
Arm Title
Quadruple Therapy
Arm Type
Experimental
Arm Description
Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin
Intervention Type
Drug
Intervention Name(s)
hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
Treatment with the drug hydroxychloroquine
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Other Intervention Name(s)
Zithromax
Intervention Description
Treatment with the drug azithromycin
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Other Intervention Name(s)
norvir
Intervention Description
Treatment with the drug ritonavir
Intervention Type
Drug
Intervention Name(s)
Lopinavir
Intervention Description
Treatment with the drug lopinavir
Primary Outcome Measure Information:
Title
Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores
Description
Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
Time Frame
6 months
Title
Efficacy of Treatment by Time to Non-Infectivity
Description
Time to non-infectivity as measured by PCR testing
Time Frame
10 days
Secondary Outcome Measure Information:
Title
Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores
Description
Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores.
Description
Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Complete Blood Count
Description
Changes in blood parameters measured in a Complete Blood Count (CBC).
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Complete Blood Count
Description
Changes in blood parameters measured in a Complete Metabolic Panel.
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel -Albumin
Description
Changes in serum albumin levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin
Description
Changes in serum albumin levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio
Description
Changes in serum albumin/globulin ratio
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio
Description
Changes in serum albumin/globulin ratio
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase
Description
Changes in serum alkaline phosphatase levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase
Description
Changes in serum alkaline phosphatase levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - AST
Description
Changes in serum AST levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - AST
Description
Changes in serum AST levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT
Description
Changes in serum ALT levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel ALT
Description
Changes in serum ALT levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio
Description
Changes in serum BUN/Creatinine Ratio
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio
Description
Changes in serum BUN/Creatinine Ratio
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN
Description
Changes in serum Blood Urea Nitrogen levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - BUN
Description
Changes in serum Blood Urea Nitrogen levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Calcium
Description
Changes in serum calcium levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium
Description
Changes in serum calcium levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide
Description
Changes in serum carbon dioxide levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide
Description
Changes in serum carbon dioxide levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Chloride
Description
Changes in serum chloride levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride
Description
Changes in serum chloride levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine
Description
Changes in serum creatinine levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine
Description
Changes in serum creatinine levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Globulin
Description
Changes in serum globulin levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin
Description
Changes in serum globulin levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose
Description
Changes in blood glucose levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Glucose
Description
Changes in blood glucose levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Potassium
Description
Changes in blood potassium levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium
Description
Changes in blood potassium levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin
Description
Changes in serum total bilirubin levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin
Description
Changes in serum total bilirubin levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein
Description
Changes in serum total protein levels
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein
Description
Changes in serum total protein levels
Time Frame
6 months
Title
Safety of Dual Therapy as Measured by Treatment Related SAE
Description
Presence or absence of treatment related serious adverse events Grade III or higher
Time Frame
6 months
Title
Safety of Quadruple Therapy as Measured by Treatment Related SAE
Description
Presence or absence of treatment related serious adverse events Grade III or higher
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent, demonstrating that the subject understands the procedures required for the study and the purpose of the study
Healthy, ambulant male or female subjects 18 years of age to 65 years of age
Positive test for COVID-19 by RT-PCR at screening
Subjects must agree to practice at least one highly effective method of birth control for the duration of the study. This includes condoms with spermicide, oral birth control pills, contraceptive implants, intra-uterine devices, or diaphragms. Subjects not of reproductive potential will be exempt (e.g. post-menopausal, surgically sterilized)
Subjects must agree they will do their best to attend the treatment facility daily for 10 days
Exclusion Criteria:
Refusal to sign informed consent form
Negative test for COVID-19 by RT-PCR at screening
Severe disease symptomatically including pneumonia, respiratory distress, tachypnea, shortness of breath, temperature > 38 degrees; pleuritic pain, or frequent cough.
Known drug allergy to any of the investigational medications
Currently taking medication with known drug interactions with investigational medications (listed in appendix)
Prescription or other antiviral medications
Any comorbidities which constitute health risk for the subject
Pregnant or lactating females;
weight < 110lb;
porphyria
established retinal disease
Inability to attend daily for 10 days
Any contraindications for treatment with hydroxychloroquine
Hypoglycemia
Known G6PD deficiency
Porphyria
Anemia
Neutropenia
Alcoholism
Myasthenia gravis
Skeletal muscle disorders
Maculopathy
Changes in visual field
Liver disease
Psoriasis
History of QT >500msec
History of torsades de pointes
Anemia from pyruvate kinase and G6PD deficiencies
Abnormal EKG with QT prolongation acquired or from birth
History of jaundice or high fevers prior to developing COVID-19
Treatment with any of the medications listed in Appendix II
Treatment with any anti-epileptic medication
Treatment with any other drug not listed that affects the QT interval
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabine Hazan, MD
Organizational Affiliation
ProgenaBiome
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thomas Borody, MD, PhD,
Organizational Affiliation
Big Corona Ltd.
Official's Role
Principal Investigator
Facility Information:
Facility Name
ProgenaBiome
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Combination Therapies to Treat COVID-19 Infection
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