Hydroxychloroquine Use in Hospitalized Patients With COVID-19: Impact on Progression to Severe or Critical Disease

The primary objective is to assess the impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Placebo

Detailed Description

This study will utilize a randomized, placebo-controlled, double-blinded design. Patients admitted with confirmed COVID-19, and at least 1 of the following: requiring oxygen supplementation (≤4 liters of oxygen via nasal cannula or increase from baseline), bilateral infiltrates on CT/CXR, age >65, diabetes, hypertension, BMI > 35, chronic lung disease, cardiovascular disease, chronic kidney disease, cancer (hematologic malignancies, lung cancer, and metastatic disease), will be randomized in a 1:1 fashion to hydroxychloroquine 400 mg PO BID x 2 doses, then 200 mg PO BID x 8 doses or placebo at a matching schedule.

• Study Type: Interventional
• Enrollment (Anticipated): 700
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted to Wellstar Kennestone Hospital
• Age 18 years or older
• Laboratory-confirmed COVID-19

• At least 1 of the following:

  1. Requiring oxygen supplementation at ≤ 4 liters via nasal cannula or increase from baseline
  2. Bilateral infiltrates on CXR or CT of chest
  3. Age 65 or older
  4. Diabetes
  5. Hypertension
  6. BMI > 35
  7. Chronic lung disease
  8. Cardiovascular disease
  9. Chronic kidney disease
  10. Cancer (hematologic malignancies, lung cancer, and metastatic disease)

Exclusion Criteria:

• Unable to provide informed consent
• Unable to take oral medication

• Severe/critical COVID-19 disease at presentation

  1. Intensive care or intermediate care required at admission or within 48 hours
  2. Requiring oxygen supplementation via high flow nasal cannula, bipap, or non-rebreather mask at admission or within 48 hours
• Likelihood of survival <48 hours in the opinion of the primary physician or transitioned to comfort measures within 48 hours of admission
• Inability to take hydroxychloroquine due to allergy, QTc > 500 ms (male) or 520 ms (female) prior to initiation of hydroxychloroquine, pre-existing retinopathy, known G6PD deficiency, known porphyria, or significant drug- drug interactions
• Pregnant or breastfeeding
• Severe liver disease (Child-Pugh Class C)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo 400 mg PO BID x 2 doses, then 200 mg PO BID x 8 doses
Experimental: Hydroxychloroquine	Drug: Hydroxychloroquine; Hydroxychloroquine 400 mg PO BID x 2 doses, then 200 mg PO BID x 8 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.	The impact will be evaluated by comparing rates of a composite primary outcome in patients randomized to hydroxychloroquine versus those randomized to placebo. The composite outcome includes progression to severe/critical disease or death (including withdrawal of care/hospice transfer). Progression to severe/critical disease is defined by requiring oxygen delivery via high flow nasal cannula, non-rebreather mask, bipap, or transfer to intensive care (ICU) or intermediate care units (IMCU) due to COVID-19-related complications.	30 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay		30 Days
30-Day Mortality		30 Days
Resolution of Symptoms	Resolution of symptoms will be assessed using standard medical interview procedures with the subject and review of the medical records.	14 Days
Incidence of QTc >500ms after initiation of therapy		30 Days
Incidence of discontinuation of therapy		30 Days

Collaborators and Investigators

• Sponsor: WellStar Health System

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2020
• Primary Completion (Anticipated): December 7, 2020
• Study Completion (Anticipated): December 7, 2020

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 11, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 1604885

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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