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.
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.
Drug: Degarelix
Degarelix is an FDA-approved drug for prostate cancer
Other: Saline
09% Saline
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.
Phoenix VA Health Care System, Phoenix, AZ
Phoenix, Arizona, United States
Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
Little Rock, Arkansas, United States
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, United States
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
Los Angeles, California, United States
Miami VA Healthcare System, Miami, FL
Miami, Florida, United States
St. Louis VA Medical Center John Cochran Division, St. Louis, MO
Saint Louis, Missouri, United States
Brooklyn Campus of the VA NY Harbor Healthcare System, Brooklyn, NY
Brooklyn, New York, United States
Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
New York, New York, United States
Philadelphia MultiService Center, Philadelphia, PA
Philadelphia, Pennsylvania, United States
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, United States
Memphis VA Medical Center, Memphis, TN
Memphis, Tennessee, United States
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, United States
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, United States
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, United States
Matthew B. Rettig, MD, Principal Investigator
VA Greater Los Angeles Healthcare System, West Los Angeles, CA