Clinical trial NCT04397718: Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2020-05-21
Enrollment: 96
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Composite of Mortality, Ongoing Need for Hospitalization, or Mechanical Ventilation at Day 15
timeFrame: 15 days
Secondary outcomes:
measure: Time to Clinical Improvement
timeFrame: Through discharge (an average of 8 days with a maximum of 2.5 months)
measure: Inpatient Mortality
timeFrame: Through discharge (an average of 8 days with a maximum of 2.5 months)
measure: Duration of Hospitalization
timeFrame: Through discharge (an average of 8 days with a maximum of 2.5 months)
measure: Duration of Intubation
timeFrame: Through discharge (an average of 8 days with a maximum of 2.5 months)
measure: Time to Normalization of Temperature.
timeFrame: Through discharge (an average of 8 days with a maximum of 2.5 months)
measure: Maximum Severity of COVID19 Illness.
timeFrame: Through discharge (an average of 8 days with a maximum of 2.5 months)
measure: Composite of Mortality, Ongoing Need for Hospitalization, or Mechanical Ventilation at Day 30
timeFrame: 30 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix VA Health Care System, Phoenix, AZ
state: Arizona
city: Little Rock
country: United States
facility: Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
state: Arkansas
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
city: Miami
country: United States
facility: Miami VA Healthcare System, Miami, FL
state: Florida
city: Saint Louis
country: United States
facility: St. Louis VA Medical Center John Cochran Division, St. Louis, MO
state: Missouri
city: Brooklyn
country: United States
facility: Brooklyn Campus of the VA NY Harbor Healthcare System, Brooklyn, NY
state: New York
city: New York
country: United States
facility: Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
state: New York
city: Philadelphia
country: United States
facility: Philadelphia MultiService Center, Philadelphia, PA
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center, Charleston, SC
state: South Carolina
city: Memphis
country: United States
facility: Memphis VA Medical Center, Memphis, TN
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center, Houston, TX
state: Texas
city: Seattle
country: United States
facility: VA Puget Sound Health Care System Seattle Division, Seattle, WA
state: Washington
Study officials:
affiliation: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
name: Matthew B. Rettig, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.