Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH)

• ClinicalTrials.gov Identifier: NCT04397718
• Recruitment Status: Completed
• First Posted: May 21, 2020
• Results First Posted: June 6, 2022
• Last Update Posted: June 6, 2022
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

The purpose of this study is to determine if temporary androgen suppression improves the clinical outcomes of Veterans who are hospitalized to an acute care ward due to COVID-19.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Degarelix; Other: Saline	Phase 2

Detailed Description:

A novel coronavirus, now termed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019. The first confirmed cases occurred in December in Wuhan, Hubei province, China. It now infects people on six continents, spreading person to person. The World Health Organization (WHO) classified it as a global pandemic on March 11, 2020. As of April 6, 2020, there are more than 1.2 million confirmed cases and more than 70,000 deaths attributed to this virus. Every person on Earth, as well as every United States Veteran, is at risk. This is the emergent public health threat of our time.

SARS-CoV-2 is a singled stranded RNA virus related to severe acute respiratory syndrome-related coronavirus (SARS-CoV-1). SARS-CoV-2 is thought to be transmissible largely by respiratory droplets or direct contact, but might also be transmitted through aerosolization. SARS-CoV-2 disease severity ranges from no to minimal symptoms, mildly symptomatic with cough and dyspnea, to severe respiratory distress with multi-organ failure requiring admission to an intensive care unit and emergent ventilator support. Although data are evolving, the severity of illness varies with age, co-existing comorbidities, and biological sex, with older age, people with pre-existing cardiovascular disease, and males manifesting greater disease severity.

A worldwide effort is in place to contain and suppress human-to-human transmission. These public-health strategies aim to slow the rate of spread and reduce the burden on critical care infrastructure. However, there is also a need effective therapeutics. Vaccine trials are underway but potential approvals are at least a year away. Development of new drugs de novo to treat SARS2-CoV-2 will likely take even longer. Thus, the most expedient therapeutic strategy to confront this pandemic will repurpose existing FDA-approved therapeutics. One potential strategy targets viral components directly, using existing antivirals and anti-infectives currently used for other diseases. Such efforts include trials of hydroxychloroquine, remdesivir, and ribavirin. Another strategy involves targeting the human proteins, rather than viral proteins, required for SARS CoV-2 entry and replication.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH): A Multicenter, Phase 2 Randomized Controlled Trial of Best Supportive Care (BSC) vs BSC Plus Degarelix
• Actual Study Start Date: July 6, 2020
• Actual Primary Completion Date: June 8, 2021
• Actual Study Completion Date: June 8, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo + BSC; No active, only placebo (2 - prefilled syringes containing 3 ml of 0.9% saline) plus best supportive care.	Other: Saline; 09% Saline
Experimental: Degarelix + BSC; Active Degarelix (2 - prefilled syringes containing 3 ml of reconstituted Degarelix concentrated to 40mg/ml) plus best supportive care.	Drug: Degarelix; Degarelix is an FDA-approved drug for prostate cancer

Outcome Measures

Primary Outcome Measures :

1. Composite of Mortality, Ongoing Need for Hospitalization, or Mechanical Ventilation at Day 15 [ Time Frame: 15 days ]
   Number of Patients who died, had a ongoing need for hospitalization, or was placed on mechanical ventilation at Day 15.

Secondary Outcome Measures :

1. Time to Clinical Improvement [ Time Frame: Through discharge (an average of 8 days with a maximum of 2.5 months) ]
   Time to clinical improvement as defined by a decline of 2 categories or more from the baseline modified 7-category ordinal scale of clinical status of hospitalized influenza patients or hospital discharge, whichever comes first. Participants whose condition worsened, who died, or who withdrew from the study without clinical improvement were censored. The 7-categories were defined as: 1: Not hospitalized with resumption of normal activities; 2: Not hospitalized, but unable to resume normal activities; 3: Hospitalization, not requiring supplemental oxygen; 4: Hospitalization, requiring supplemental oxygen; 5: Hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6: Hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 7: Death.
2. Inpatient Mortality [ Time Frame: Through discharge (an average of 8 days with a maximum of 2.5 months) ]
   Number of patients who died during their hospital stay
3. Duration of Hospitalization [ Time Frame: Through discharge (an average of 8 days with a maximum of 2.5 months) ]
   Length of hospital stay (randomization to discharge)
4. Duration of Intubation [ Time Frame: Through discharge (an average of 8 days with a maximum of 2.5 months) ]
   Length of time on mechanical ventilation. Length of mechanical ventilation imputed to maximum length (50 days) for patients who died on mechanical ventilation or who were on mechanical ventilation, but date removed was unknown. Length of mechanical ventilation imputed to 0 for patients never on mechanical ventilation.
5. Time to Normalization of Temperature. [ Time Frame: Through discharge (an average of 8 days with a maximum of 2.5 months) ]
   Length of time for temperature to be less than < 37.5 degree Celsius for 48 hours
6. Maximum Severity of COVID19 Illness. [ Time Frame: Through discharge (an average of 8 days with a maximum of 2.5 months) ]
   Maximum severity score on the modified 7-category ordinal scale of clinical status of hospitalized influenza patients. The 7-categories were defined as: 1: Not hospitalized with resumption of normal activities; 2: Not hospitalized, but unable to resume normal activities; 3: Hospitalization, not requiring supplemental oxygen; 4: Hospitalization, requiring supplemental oxygen; 5: Hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6: Hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 7: Death.
7. Composite of Mortality, Ongoing Need for Hospitalization, or Mechanical Ventilation at Day 30 [ Time Frame: 30 days ]
   Number of Patients who died, had a ongoing need for hospitalization, or was placed on mechanical ventilation at Day 30.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male Veterans admitted to a VA hospital.
• Age > 18
• Hospitalized on an acute care ward with a diagnosis of COVID-19 contributing to hospitalization.
• Positive RT-PCR assay for SARS-CoV-2 on a nasopharyngeal swab sample.
• Severity of illness of level 3, 4 or 5 on the influenza severity scale (see Appendix A) at the time of randomization.
• The subject (or legally acceptable representative if applicable) must provide written informed consent for the trial.

Exclusion Criteria:

• History of severe hypersensitivity to degarelix or any component of their respective formulation.
• History of congenital long QT syndrome or known history of prolonged QT interval corrected by the Fridericia correction formula (QTcF) > 500 msec on electrocardiogram performed at screening.
• Planned discharge within 24 hours of treatment initiation.
• Subject is planning to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.

• Ongoing usage of a Class IA or Class III antiarrhythmic agent. At least 5 half lives must elapse since any prior use of a Class IA or III antiarrhythmic agent prior to administration of study drug.

  --Baseline electrolyte abnormalities of Grade 3 or higher (based on CTCAE v5.0 criteria). Patients may be included if baseline electrolyte abnormalities are corrected to Grade 2 or lower prior to study drug administration.

• Myocardial infarction in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease.
• Enrollment in another investigational study within 30 days of Day 1.
• Known psychiatric or substance abuse disorder that would interfere with the requirements of the trial.
• Child-Pugh Class C liver disease.

• Use of any of the following hormonal agents within Day 1 of treatment:

  1. Androgen receptor antagonists or agonists within 4 weeks,
  2. Ketoconazole or abiraterone acetate within 2 weeks,
  3. Estrogens or progestins within 2 weeks,
  4. Herbal products that contain hormonally active agents within 2 weeks.
• Unwilling or unable to comply with the study protocol.
• Any condition, which in the opinion of the investigator, would preclude participation in the trial.

Contacts and Locations

Locations

United States, Arizona

Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, United States, 85012

United States, Arkansas

Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR

Little Rock, Arkansas, United States, 72205-5484

United States, California

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States, 90822

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Los Angeles, California, United States, 90073

United States, Florida

Miami VA Healthcare System, Miami, FL

Miami, Florida, United States, 33125

United States, Missouri

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

Saint Louis, Missouri, United States, 63106

United States, New York

Brooklyn Campus of the VA NY Harbor Healthcare System, Brooklyn, NY

Brooklyn, New York, United States, 11209

Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY

New York, New York, United States, 10010

United States, Pennsylvania

Philadelphia MultiService Center, Philadelphia, PA

Philadelphia, Pennsylvania, United States, 19106

United States, South Carolina

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States, 29401-5799

United States, Tennessee

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, United States, 38104

United States, Texas

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, United States, 75216

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States, 77030

United States, Washington

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States, 98108

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Matthew B. Rettig, MD; VA Greater Los Angeles Healthcare System, West Los Angeles, CA

  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:

Study Protocol  [PDF] February 9, 2021

Statistical Analysis Plan  [PDF] August 5, 2021

More Information

Publications of Results:

Nickols NG, Mi Z, DeMatt E, Biswas K, Clise CE, Huggins JT, Maraka S, Ambrogini E, Mirsaeidi MS, Levin ER, Becker DJ, Makarov DV, Adorno Febles V, Belligund PM, Al-Ajam M, Muthiah MP, Montgomery RB, Robinson KW, Wong YN, Bedimo RJ, Villareal RC, Aguayo SM, Schoen MW, Goetz MB, Graber CJ, Bhattacharya D, Soo Hoo G, Orshansky G, Norman LE, Tran S, Ghayouri L, Tsai S, Geelhoed M, Rettig MB. Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial. JAMA Netw Open. 2022 Apr 1;5(4):e227852. doi: 10.1001/jamanetworkopen.2022.7852.

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

Nickols NG, Goetz MB, Graber CJ, Bhattacharya D, Soo Hoo G, Might M, Goldstein DB, Wang X, Ramoni R, Myrie K, Tran S, Ghayouri L, Tsai S, Geelhoed M, Makarov D, Becker DJ, Tsay JC, Diamond M, George A, Al-Ajam M, Belligund P, Montgomery RB, Mostaghel EA, Sulpizio C, Mi Z, Dematt E, Tadalan J, Norman LE, Briones D, Clise CE, Taylor ZW, Huminik JR, Biswas K, Rettig MB. Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial. Trials. 2021 Jul 5;22(1):431. doi: 10.1186/s13063-021-05389-0.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT04397718
• Other Study ID Numbers: COVID19-8900-15
• First Posted: May 21, 2020
• Results First Posted: June 6, 2022
• Last Update Posted: June 6, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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.: Yes

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases