A Study of Combination Therapies to Treat COVID-19 Infection

Phase 2

Withdrawn

• Conditions: SARS Pneumonia; Corona Virus Infection; Coronavirus Infection; Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere; Coronavirus-19; COVID; SARS-CoV 2; COVID-19
• Interventions: Drug: hydroxychloroquine; Drug: Azithromycin; Drug: Ritonavir; Drug: Lopinavir

• Registration Number: NCT04459702
• Lead Sponsor: ProgenaBiome

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

Study Timeline

• Study First Submitted: 2020-06-25
• Study Start: 2020-07
• Study First Submitted QC: 2020-07-04
• Study First Posted: 2020-07-07
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-06
• Last Update Posted: 2021-04-08
• Primary Completion: 2021-07
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Quadruple Therapy	Lopinavir	Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin
Dual Therapy	hydroxychloroquine	Dual Therapy utilizing hydroxychloroquine and azithromycin.
Dual Therapy	Azithromycin	Dual Therapy utilizing hydroxychloroquine and azithromycin.
Quadruple Therapy	Azithromycin	Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin
Quadruple Therapy	hydroxychloroquine	Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin
Quadruple Therapy	Ritonavir	Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin

Primary Outcome Measures

Name	Time	Method
Efficacy of Treatment by Time to Non-Infectivity	10 days	Time to non-infectivity as measured by PCR testing
Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores	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.

Secondary Outcome Measures

Name	Time	Method
Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio	6 months	Changes in serum albumin/globulin ratio
Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase	6 months	Changes in serum alkaline phosphatase levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN	6 months	Changes in serum Blood Urea Nitrogen levels
Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores.	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.
Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase	6 months	Changes in serum alkaline phosphatase levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - AST	6 months	Changes in serum AST levels
Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide	6 months	Changes in serum carbon dioxide levels
Safety of Dual Therapy as Measured by Metabolic Panel -Albumin	6 months	Changes in serum albumin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin	6 months	Changes in serum albumin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio	6 months	Changes in serum BUN/Creatinine Ratio
Safety of Dual Therapy as Measured by Metabolic Panel - BUN	6 months	Changes in serum Blood Urea Nitrogen levels
Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin	6 months	Changes in serum total bilirubin levels
Safety of Dual Therapy as Measured by Treatment Related SAE	6 months	Presence or absence of treatment related serious adverse events Grade III or higher
Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores	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.
Safety of Dual Therapy as Measured by Complete Blood Count	6 months	Changes in blood parameters measured in a Complete Blood Count (CBC).
Safety of Quadruple Therapy as Measured by Complete Blood Count	6 months	Changes in blood parameters measured in a Complete Metabolic Panel.
Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio	6 months	Changes in serum albumin/globulin ratio
Safety of Dual Therapy as Measured by Metabolic Panel - AST	6 months	Changes in serum AST levels
Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio	6 months	Changes in serum BUN/Creatinine Ratio
Safety of Dual Therapy as Measured by Metabolic Panel - Calcium	6 months	Changes in serum calcium levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium	6 months	Changes in serum calcium levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose	6 months	Changes in blood glucose levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium	6 months	Changes in blood potassium levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein	6 months	Changes in serum total protein levels
Safety of Quadruple Therapy as Measured by Treatment Related SAE	6 months	Presence or absence of treatment related serious adverse events Grade III or higher
Safety of Dual Therapy as Measured by Metabolic Panel - Chloride	6 months	Changes in serum chloride levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT	6 months	Changes in serum ALT levels
Safety of Dual Therapy as Measured by Metabolic Panel ALT	6 months	Changes in serum ALT levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine	6 months	Changes in serum creatinine levels
Safety of Dual Therapy as Measured by Metabolic Panel - Globulin	6 months	Changes in serum globulin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin	6 months	Changes in serum total bilirubin levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide	6 months	Changes in serum carbon dioxide levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride	6 months	Changes in serum chloride levels
Safety of Dual Therapy as Measured by Metabolic Panel - Glucose	6 months	Changes in blood glucose levels
Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine	6 months	Changes in serum creatinine levels
Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin	6 months	Changes in serum globulin levels
Safety of Dual Therapy as Measured by Metabolic Panel - Potassium	6 months	Changes in blood potassium levels
Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein	6 months	Changes in serum total protein levels

Trial Locations

Locations (1)

ProgenaBiome; 🇺🇸 Ventura, California, United States