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A Study of Combination Therapies to Treat COVID-19 Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04459702
Recruitment Status : Withdrawn (Was never started)
First Posted : July 7, 2020
Last Update Posted : April 8, 2021
Sponsor:
Collaborator:
Big Corona Ltd.
Information provided by (Responsible Party):
ProgenaBiome

Study Description
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This study seeks to determine whether dual or quadruple therapy is more effective in treating COVID-19.

Condition or disease Intervention/treatment Phase
COVID COVID-19 Corona Virus Infection Coronavirus Infection Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere Coronavirus-19 SARS-CoV 2 SARS Pneumonia Drug: hydroxychloroquine Drug: Azithromycin Drug: Ritonavir Drug: Lopinavir Phase 2

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
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIa Randomized, Controlled Study of Combination Therapies to Treat COVID-19 Infection
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dual Therapy
Dual Therapy utilizing hydroxychloroquine and azithromycin.
 Drug: hydroxychloroquine
Treatment with the drug hydroxychloroquine
Other Name: Plaquenil

Drug: Azithromycin
Treatment with the drug azithromycin
Other Name: Zithromax
Experimental: Quadruple Therapy
Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin
 Drug: hydroxychloroquine
Treatment with the drug hydroxychloroquine
Other Name: Plaquenil

Drug: Azithromycin
Treatment with the drug azithromycin
Other Name: Zithromax

Drug: Ritonavir
Treatment with the drug ritonavir
Other Name: norvir

Drug: Lopinavir
Treatment with the drug lopinavir


Outcome Measures
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Primary Outcome Measures :
  1. Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores [ Time Frame: 6 months ]
    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.

  2. Efficacy of Treatment by Time to Non-Infectivity [ Time Frame: 10 days ]
    Time to non-infectivity as measured by PCR testing


Secondary Outcome Measures :
  1. Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores [ Time Frame: 6 months ]
    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.

  2. Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores. [ Time Frame: 6 months ]
    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.

  3. Safety of Dual Therapy as Measured by Complete Blood Count [ Time Frame: 6 months ]
    Changes in blood parameters measured in a Complete Blood Count (CBC).

  4. Safety of Quadruple Therapy as Measured by Complete Blood Count [ Time Frame: 6 months ]
    Changes in blood parameters measured in a Complete Metabolic Panel.

  5. Safety of Dual Therapy as Measured by Metabolic Panel -Albumin [ Time Frame: 6 months ]
    Changes in serum albumin levels

  6. Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin [ Time Frame: 6 months ]
    Changes in serum albumin levels

  7. Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio [ Time Frame: 6 months ]
    Changes in serum albumin/globulin ratio

  8. Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio [ Time Frame: 6 months ]
    Changes in serum albumin/globulin ratio

  9. Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase [ Time Frame: 6 months ]
    Changes in serum alkaline phosphatase levels

  10. Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase [ Time Frame: 6 months ]
    Changes in serum alkaline phosphatase levels

  11. Safety of Dual Therapy as Measured by Metabolic Panel - AST [ Time Frame: 6 months ]
    Changes in serum AST levels

  12. Safety of Quadruple Therapy as Measured by Metabolic Panel - AST [ Time Frame: 6 months ]
    Changes in serum AST levels

  13. Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT [ Time Frame: 6 months ]
    Changes in serum ALT levels

  14. Safety of Dual Therapy as Measured by Metabolic Panel ALT [ Time Frame: 6 months ]
    Changes in serum ALT levels

  15. Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio [ Time Frame: 6 months ]
    Changes in serum BUN/Creatinine Ratio

  16. Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio [ Time Frame: 6 months ]
    Changes in serum BUN/Creatinine Ratio

  17. Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN [ Time Frame: 6 months ]
    Changes in serum Blood Urea Nitrogen levels

  18. Safety of Dual Therapy as Measured by Metabolic Panel - BUN [ Time Frame: 6 months ]
    Changes in serum Blood Urea Nitrogen levels

  19. Safety of Dual Therapy as Measured by Metabolic Panel - Calcium [ Time Frame: 6 months ]
    Changes in serum calcium levels

  20. Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium [ Time Frame: 6 months ]
    Changes in serum calcium levels

  21. Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide [ Time Frame: 6 months ]
    Changes in serum carbon dioxide levels

  22. Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide [ Time Frame: 6 months ]
    Changes in serum carbon dioxide levels

  23. Safety of Dual Therapy as Measured by Metabolic Panel - Chloride [ Time Frame: 6 months ]
    Changes in serum chloride levels

  24. Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride [ Time Frame: 6 months ]
    Changes in serum chloride levels

  25. Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine [ Time Frame: 6 months ]
    Changes in serum creatinine levels

  26. Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine [ Time Frame: 6 months ]
    Changes in serum creatinine levels

  27. Safety of Dual Therapy as Measured by Metabolic Panel - Globulin [ Time Frame: 6 months ]
    Changes in serum globulin levels

  28. Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin [ Time Frame: 6 months ]
    Changes in serum globulin levels

  29. Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose [ Time Frame: 6 months ]
    Changes in blood glucose levels

  30. Safety of Dual Therapy as Measured by Metabolic Panel - Glucose [ Time Frame: 6 months ]
    Changes in blood glucose levels

  31. Safety of Dual Therapy as Measured by Metabolic Panel - Potassium [ Time Frame: 6 months ]
    Changes in blood potassium levels

  32. Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium [ Time Frame: 6 months ]
    Changes in blood potassium levels

  33. Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin [ Time Frame: 6 months ]
    Changes in serum total bilirubin levels

  34. Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin [ Time Frame: 6 months ]
    Changes in serum total bilirubin levels

  35. Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein [ Time Frame: 6 months ]
    Changes in serum total protein levels

  36. Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein [ Time Frame: 6 months ]
    Changes in serum total protein levels

  37. Safety of Dual Therapy as Measured by Treatment Related SAE [ Time Frame: 6 months ]
    Presence or absence of treatment related serious adverse events Grade III or higher

  38. Safety of Quadruple Therapy as Measured by Treatment Related SAE [ Time Frame: 6 months ]
    Presence or absence of treatment related serious adverse events Grade III or higher


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent, demonstrating that the subject understands the procedures required for the study and the purpose of the study
  2. Healthy, ambulant male or female subjects 18 years of age to 65 years of age
  3. Positive test for COVID-19 by RT-PCR at screening
  4. 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)
  5. Subjects must agree they will do their best to attend the treatment facility daily for 10 days

Exclusion Criteria:

  1. Refusal to sign informed consent form
  2. Negative test for COVID-19 by RT-PCR at screening
  3. Severe disease symptomatically including pneumonia, respiratory distress, tachypnea, shortness of breath, temperature > 38 degrees; pleuritic pain, or frequent cough.
  4. Known drug allergy to any of the investigational medications
  5. Currently taking medication with known drug interactions with investigational medications (listed in appendix)
  6. Prescription or other antiviral medications
  7. Any comorbidities which constitute health risk for the subject
  8. Pregnant or lactating females;
  9. weight < 110lb;
  10. porphyria
  11. established retinal disease
  12. Inability to attend daily for 10 days

  13. Any contraindications for treatment with hydroxychloroquine

    1. Hypoglycemia
    2. Known G6PD deficiency
    3. Porphyria
    4. Anemia
    5. Neutropenia
    6. Alcoholism
    7. Myasthenia gravis
    8. Skeletal muscle disorders
    9. Maculopathy
    10. Changes in visual field
    11. Liver disease
    12. Psoriasis
    13. History of QT >500msec
    14. History of torsades de pointes
  14. Anemia from pyruvate kinase and G6PD deficiencies
  15. Abnormal EKG with QT prolongation acquired or from birth
  16. History of jaundice or high fevers prior to developing COVID-19
  17. Treatment with any of the medications listed in Appendix II
  18. Treatment with any anti-epileptic medication
  19. Treatment with any other drug not listed that affects the QT interval
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04459702


Locations
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United States, California
ProgenaBiome
Ventura, California, United States, 93003
Sponsors and Collaborators
ProgenaBiome
Big Corona Ltd.
Investigators
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Principal Investigator: Sabine Hazan, MD ProgenaBiome
Principal Investigator: Thomas Borody, MD, PhD, Big Corona Ltd.
More Information
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Responsible Party: ProgenaBiome
ClinicalTrials.gov Identifier: NCT04459702    
Other Study ID Numbers: PRG-043
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: April 8, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Ritonavir
Lopinavir
Azithromycin
 Hydroxychloroquine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents