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The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19

Phase 2
Conditions
2019 Novel Coronavirus
Interventions
Other: standard of care (SOC) for COVID-19
Registration Number
NCT05113810
Lead Sponsor
Ministry of Health Jordan
Brief Summary

This is a pilot, randomized, single-center, parallel group, open-label controlled study to evaluate the feasibility, safety, efficacy, and pharmacokinetics of nebulized HCQ01 plus Standard of Care (SOC) versus SOC alone in hospitalized COVID-19 patients. The Jordanian Ministry of Health (MOH) is the study sponsor, and the study will be conducted at MOH COVID-19 hospitals.

Approximately 110 patients, ≥18 years of age with a confirmed SARS-CoV-2 infection, will be enrolled and randomized 1:1 to the treatment and control arms where they will receive ten doses of Hydroxychloroquine solution via nebulizer in addition to SOC or the control arm where treatment will follow the MOH SOC.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
110
Inclusion Criteria
  1. Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at screening.
  2. Patients with a history of retinopathy, sickle cell disease or trait, psoriasis, porphyria, history of splenectomy, mental illness or uncontrolled seizures disorder, known active tuberculosis or history of incompletely treated tuberculosis, patients on chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants.
  3. Patients admitted in ICU.
  4. Taking medications which may lead to interactions with hydroxychloroquine, including penicillamine, telbivudine, botulinum toxin, fluconazole, digoxin, propafenone , cimetidine, statins, warfarin, and cyclosporine within 2 weeks of dosing start, and during the duration of the study.
  5. History of Glucose-6-phosphate dehydrogenase deficiency.
  6. Pre-treatment corrected QT interval (QTc) ≥450 milliseconds.
Exclusion Criteria
  1. Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at screening.

  2. Patients with a history of retinopathy, sickle cell disease or trait, psoriasis, porphyria, history of splenectomy, mental illness or uncontrolled seizures disorder, known active tuberculosis or history of incompletely treated tuberculosis, patients on chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants.

  3. Patients admitted in ICU.

  4. Taking medications which may lead to interactions with hydroxychloroquine, including penicillamine, telbivudine, botulinum toxin, fluconazole, digoxin, propafenone , cimetidine, statins, warfarin, and cyclosporine within 2 weeks of dosing start, and during the duration of the study.

  5. History of Glucose-6-phosphate dehydrogenase deficiency.

  6. Pre-treatment corrected QT interval (QTc) ≥450 milliseconds.

  7. Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR<30 mL/min/1.73 m2 or hemodialysis).

  8. Liver Child-Pugh grade C.

  9. Patients with Hypokalemia (<3.5mmol/L), Hypocalcemia (<2.2mmol/L), Hypomagnesemia (<0.66mmol/L). Will be included after correction.

  10. Need for mechanical ventilation.

  11. History of hypersensitivity to hydroxychloroquine.

  12. History of Chronic Hepatitis B or hepatitis C infections.

  13. History of Human Immunodeficiency Virus (HIV) infection.

  14. Concurrent serious illness including, but not limited to, any of the following:

    • Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, or unstable angina).
    • New York Heart Association class II-IV congestive heart failure.
    • Serious cardiac arrhythmia requiring medication. -Peripheral vascular disease ≥ grade 2 within the past year. -
    • Psychiatric illness/social situation that would limit compliance with study requirements. -COPD, Lung cancer, and moderate to severe asthma.
  15. Any other significant finding based on the judgment of the PI would increase the risk of having an adverse outcome from participating in this study.

  16. Any other concomitant treatment based on the judgment of the PI would increase the risk of having an adverse outcome from participating in this study.

  17. Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 80 days of signing the informed consent/assent for this current trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
First Arm (Hydroxychloroquine sulfate, 5 days)HCQ01Participants will receive continued standard of care therapy (SOC) for COVID-19 together with 2 ml HCQ01 (12.5 mg/ml) twice a day for 5 consecutive days.
Second Arm (Continued Standard of Care (SOC) Therapy)standard of care (SOC) for COVID-19Participants will receive continued standard of care therapy for COVID-19
Primary Outcome Measures
NameTimeMethod
WHO Ordinal Scale for for Clinical Improvement[ Day -1 (screening) to Days 3,6, and 14 ]

Change in condition measured using the Ordinal Scale for Clinical Improvement. Patients are scored on a scale of 0-10 with 0 being uninfected and 10 being dead

Secondary Outcome Measures
NameTimeMethod
Proportion of participants who improve by at least one level lower on the 11-point WHO-OSCIDay 28
All-cause mortalityDay 28
HCQ concentration in plasma versus time profilesDay 1 pre-dose (within 1-hour prior dosing) and +2, +5, +10, +15, +20, +25, and +30 minutes after dose, and also +1, +2, +3, +4 and +6 hours post-dose completion
Cardiac Arrhythmia - Lengthening QTcUp to day 6

Cardiologist Diagnostic Documentation

Change from Baseline Oxygenation as determined by the SpO2/FiO2 ratioDays 3 & 6
Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia [Time FrameUp to day 6

Cardiologist Diagnostic Documentation

Rate of Transfer to the Intensive Care UnitUp to day 28
Time to Hospital Discharge or NEWS2 (National Early Warning Score 2) of ≤ 2Up to day 28
Treatment-related adverse events of HCQUp to day 28
Cardiac Arrhythmia - Ventricular TachycardiaUp to day 6

Cardiologist Diagnostic Documentation

Trial Locations

Locations (1)

Prince Hamza Hospital/ Amman Field Hospital

🇯🇴

Amman, Jordan

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