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

• ClinicalTrials.gov Identifier: NCT04397718
• Recruitment Status: Recruiting
• First Posted: May 21, 2020
• Last Update Posted: March 8, 2021
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Tracking Information

• First Submitted Date: May 14, 2020
• First Posted Date: May 21, 2020
• Last Update Posted Date: March 8, 2021
• Actual Study Start Date: July 6, 2020
• Estimated Primary Completion Date: July 6, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 19, 2020)

A composite endpoint of mortality, ongoing need for hospitalization, or requirement for mechanical ventilation/extracorporeal membrane oxygenation (ECMO) at Day 15 after randomization. [ Time Frame: 15 days ]

Determine if degarelix + best supportive care (BSC) as compared to placebo + BSC reduces the composite endpoint of mortality, ongoing need for hospitalization, or requirement for mechanical ventilation/extracorporeal membrane oxygenation (ECMO) at Day 15 after randomization.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 2, 2020)

• Time to clinical improvement [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces time to clinical improvement as defined by a decline of 2 categories or more from the baseline on the modified 7-category ordinal scale of clinical status of hospitalized influenza patients or hospital discharge whichever comes first.
• Inpatient mortality [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces inpatient mortality.
• Duration of hospitalization [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC shortens the duration of hospitalization.
• Duration of intubation for mechanical ventilation. [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC shortens the duration of intubation for mechanical ventilation.
• Time to normalization of temperature. [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces the time to normalization of temperature (T < 37.5 for 48 hours)
• Maximum severity of COVID19 illness. [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces the maximum severity of COVID-19 illness based on the modified 7-category ordinal scale of clinical status of hospitalized influenza patients. Score range 1-7, higher scores equals worse outcome.
• A composite endpoint of mortality, ongoing need for hospitalization, or requirement for mechanical ventilation/extracorporeal membrane oxygenation (ECMO) at Day 30 after randomization. [ Time Frame: 30 days ]
  Determine if degarelix + best supportive care (BSC) as compared to placebo + BSC reduces the composite endpoint of mortality, ongoing need for hospitalization, or requirement for mechanical ventilation/extracorporeal membrane oxygenation (ECMO) at Day 30 after randomization.

Original Secondary Outcome Measures (submitted: May 19, 2020)

• Time to clinical improvement [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces time to clinical improvement as defined by a decline of 2 categories or more from the baseline on the modified 7-category ordinal scale of clinical status of hospitalized influenza patients
• Inpatient mortality [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces inpatient mortality.
• Duration of hospitalization [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC shortens the duration of hospitalization.
• Duration of intubation for mechanical ventilation. [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC shortens the duration of intubation for mechanical ventilation.
• Time to normalization of temperature. [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces the time to normalization of temperature (T < 37.5 for 48 hours)
• Maximum severity of COVID19 illness. [ Time Frame: Through study completion/discharge (an average of 30 days with a maximum of 4 months) ]
  Determine if degarelix + BSC as compared to placebo + BSC reduces the maximum severity of COVID-19 illness based on the modified 7-category ordinal scale of clinical status of hospitalized influenza patients. Score range 1-7, higher scores equals worse outcome.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: Degarelix
  Degarelix is an FDA-approved drug for prostate cancer
• Other: Saline
  09% Saline

Study Arms

• Placebo Comparator: Placebo + BSC
  No active, only placebo (2 - prefilled syringes containing 3 ml of 0.9% saline) plus best supportive care.
  Intervention: Other: Saline
• Experimental: Degarelix + BSC
  Active Degarelix (2 - prefilled syringes containing 3 ml of reconstituted Degarelix concentrated to 40mg/ml) plus best supportive care.
  Intervention: Drug: Degarelix

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 19, 2020): 198
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 6, 2021
• Estimated Primary Completion Date: July 6, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Matthew B Rettig, MD; (310) 478-3711; matthew.rettig@va.gov

Contact: Nicholas G Nickols, MD PhD; (310) 478-3711; nicholas.nickols@va.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04397718
• Other Study ID Numbers: COVID19-8900-15
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: VA Office of Research and Development
• Study Sponsor: VA Office of Research and Development
• Collaborators: Not Provided

Investigators

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

• PRS Account: VA Office of Research and Development
• Verification Date: March 2021