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

• ClinicalTrials.gov Identifier: NCT04329832
• Recruitment Status: Completed
• First Posted: April 1, 2020
• Results First Posted: April 20, 2022
• Last Update Posted: April 20, 2022
• 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
• Actual Primary Completion Date: July 1, 2020
• Actual Study Completion Date: January 1, 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) ]
   Improvement of clinical condition of the patient defined by the COVID-19 WHO ordinal Outcomes score. 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 [ Time Frame: Admission (day 1) to 28 days after admission (day 28) ]
   Calculated as number of days patient not in hospital
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 number of days that patient is not on a ventilator up to day 28 days after admission
3. ICU-free Days at 28 Days [ Time Frame: Admission (day 1) to 28 days after admission (day 28) ]
   Calculated as number of days patient not in an ICU
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) ]
   Time to 1-point decrease in the WHO ordinal recovery score is defined as the number of days until the ordinal outcome score drops by 1 relative to baseline on the 8-point WHO COVID Ordinal Outcomes scale, which 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".

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.

  Study Documents (Full-Text)

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

Study Protocol  [PDF] April 25, 2020

Statistical Analysis Plan  [PDF] June 29, 2020

More Information

Additional Information:

Source for WHO COVID Ordinal Outcomes Scale 

Publications:

WHO, 2020. WHO R&D Blueprint, novel Coronavirus, COVID-19 Therapeutic Trial Synopsis. https://www.who.int/publications/i/item/covid-19-therapeutic-trial-synopsis

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

Koric A, Chang CP, Mark B, Rowe K, Snyder J, Dodson M, Deshmukh VG, Newman MG, Fraser AM, Smith KR, Date AP, Gren LH, Porucznik CA, Haaland BA, Henry NL, Hashibe M. Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study. Cancer. 2022 Jul 15;128(14):2826-2835. doi: 10.1002/cncr.34224. Epub 2022 May 13.

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;18(4):590-7. doi: 10.1513/AnnalsATS.202008-940OC. Online 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
• Results First Posted: April 20, 2022
• Last Update Posted: April 20, 2022
• Last Verified: April 2022

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