Hydroxychloroquine vs. Azithromycin for Hospitalized Patients With Suspected or Confirmed COVID-19 (HAHPS)

• ClinicalTrials.gov Identifier: NCT04329832
• Recruitment Status: Active, not recruiting
• First Posted: April 1, 2020
• Last Update Posted: September 2, 2020
• Sponsor: Intermountain Health Care, Inc.
• Collaborator: University of Utah
• Information provided by (Responsible Party): Samuel Brown, Intermountain Health Care, Inc.

Study Description

Brief Summary:

This study will compare two drugs (hydroxychloroquine and azithromycin) to see if hydroxychloroquine is better than azithromycin in treating hospitalized patients with suspected or confirmed COVID-19.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Hydroxychloroquine; Drug: Azithromycin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hydroxychloroquine vs. Azithromycin for Hospitalized Patients With Suspected or Confirmed COVID-19 (HAHPS): A Prospective Pragmatic Trial
• Actual Study Start Date: March 30, 2020
• Estimated Primary Completion Date: December 18, 2020
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Hydroxychloroquine	Drug: Hydroxychloroquine; Patients in the hydroxychloroquine arm will receive hydroxychloroquine 400 mg by mouth twice daily for 1 day, then 200 mg by mouth twice daily for 4 days (dose reductions for weight < 45 kg or GFR (glomerular filtration rate)<50ml/min). For patients < 45kg, doses will be halved. For patients with GFR<50ml/min, the final dose of hydroxychloroquine will not be administered. If the patient has already received hydroxychloroquine prior to randomization (no more than 2 days), the prior doses will count toward the 5-day total.
Active Comparator: Azithromycin	Drug: Azithromycin; Patients in the azithromycin arm will receive azithromycin 500 mg on day 1 plus 250 mg daily on days 2-5 (may be administered intravenously per clinician preference). If the patient has already received azithromycin prior to randomization (no more than 2 days), the prior doses will count toward the 5-day total.

Outcome Measures

Primary Outcome Measures :

1. COVID Ordinal Outcomes Scale at 14 days [ Time Frame: Assessed once on day 14 after enrollment (enrollment is day 0) ]
   Per https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf, this scale reflects a range from uninfected to dead, where 0 is "no clinical or virological evidence of infection", 1 is "no limitation of activities", 2 is "limitation of activities", 3 is "hospitalized, no oxygen therapy", 4 is "oxygen by mask or nasal prongs", 5 is "non-invasive ventilation or high-flow oxygen", 6 is "intubation and mechanical ventilation", 7 is "ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)", and 8 is "death".

Secondary Outcome Measures :

1. Hospital-free days at 28 days (number of days patient not in hospital) [ Time Frame: Admission (day 1) to 28 days after admission (day 28) ]
   Calculated as a worst-rank ordinal (death is counted as -1 days).
2. Ventilator-free days at 28 days (number of days patient not on a ventilator) [ Time Frame: Admission (day 1) to 28 days after admission (day 28) ]
   Calculated as a worst-rank ordinal (death is counted as -1 days).
3. ICU-free days at 28 days (number of days patient not in an ICU) [ Time Frame: Admission (day 1) to 28 days after admission (day 28) ]
   Calculated as a worst-rank ordinal (death is counted as -1 days).
4. Time to a 1-point decrease in the WHO ordinal recovery score [ Time Frame: Admission (day 1) to 14 days after admission (day 14) ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Adult (age ≥ 18 years)

• Confirmed OR suspected COVID-19,

  • Confirmed: Positive assay for COVID-19 within the last 10 days
  • Suspected: Pending assay for COVID-19 WITH high clinical suspicion
• Scheduled for admission or already admitted to an inpatient bed

Exclusion Criteria:

• Allergy to hydroxychloroquine or azithromycin
• History of bone marrow transplant
• Known G6PD deficiency
• Chronic hemodialysis or Glomerular Filtration Rate < 20ml/min
• Psoriasis
• Porphyria
• Concomitant use of digitalis, flecainide, amiodarone, procainamide, propafenone, cimetidine, dofetilide, phenobarbital, phenytoin, or sotalol
• Known history of long QT syndrome
• Current known QTc>500 msec
• Pregnant or nursing
• Prisoner
• Weight < 35kg
• Seizure disorder
• Severe liver disease
• Outpatient use of hydroxychloroquine for treatment of a disease other than COVID-19 OR has received more than 2 days of hydroxychloroquine or azithromycin for suspected or confirmed COVID-19
• Patient has recovered from COVID-19 and/or is being discharged from the hospital on day of enrollment.
• Treating physician refuses to allow patient participation in the study
• Unable to obtain informed consent
• Prior enrollment in this study

Contacts and Locations

Locations

United States, Utah

Intermountain Medical Center

Murray, Utah, United States, 84107

University of Utah

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

Intermountain Health Care, Inc.

University of Utah

Investigators

• Principal Investigator: Samuel M Brown, MD MS; Intermountain Health Care, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Brown SM, Peltan I, Kumar N, Leither L, Webb BJ, Starr N, Grissom CK, Buckel WR, Srivastava R, Butler AM, Groat D, Haaland B, Ying J, Harris E, Johnson S, Paine R 3rd, Greene T. Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial. Ann Am Thorac Soc. 2020 Nov 9. doi: 10.1513/AnnalsATS.202008-940OC. [Epub ahead of print]

Brown SM, Peltan ID, Webb B, Kumar N, Starr N, Grissom C, Buckel WR, Srivastava R, Harris ES, Leither LM, Johnson SA, Paine R 3rd, Greene T. Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial. Ann Am Thorac Soc. 2020 Aug;17(8):1008-1015. doi: 10.1513/AnnalsATS.202004-309SD.

• Responsible Party: Samuel Brown, Director, Critical Care Research, Intermountain Health Care, Inc.
• ClinicalTrials.gov Identifier: NCT04329832
• Other Study ID Numbers: 1051355
• First Posted: April 1, 2020
• Last Update Posted: September 2, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: In order to protect patient privacy and comply with relevant regulations, identified data are unavailable. Requests for deidentified data from qualified researchers with appropriate ethics board approvals and relevant data use agreements will be processed by the Intermountain Office of Research, officeofresearch@imail.org.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Samuel Brown, Intermountain Health Care, Inc.:

SARS-CoV-2; Hydroxychloroquine; Azithromycin

Additional relevant MeSH terms:

COVID-19; Azithromycin; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Hydroxychloroquine; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents