Clinical trial NCT04577001: Letrozole in Patients With Hepatopulmonary Syndrome
Official title: Letrozole in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatopulmonary Syndrome
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
First posted: 2020-10-06
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
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 assess the safety, tolerability and possible benefit of letrozole compared to placebo in patients with Hepatopulmonary Syndrome.

Detailed description: This study is a phase II randomized, double-blind, placebo-controlled parallel trial of 20 subjects with hepatopulmonary syndrome designed to assess the effect of letrozole 2.5 mg orally daily or placebo for 6 months on the alveolar-arterial oxygen gradient (AaPO2).

Subjects at each site will be screened at outpatient clinic visit appointments and interested qualified subjects will be consented and offered participation in this trial. Once consent has been obtained baseline values will be established and subjects will begin letrozole with follow-up clinic visits and testing at 3 months, and 6 months.

Eligibility criteria: Inclusion Criteria

* Diagnosis of moderate to very severe hepatopulmonary syndrome which consists of having all 3 of the following conditions:

  * Presence of liver disease or portal hypertension
  * Intrapulmonary shunting on contrast-enhanced echocardiogram
  * Hypoxemia \[A-a gradient ≥15mmHg (or ≥20mmHg if age \>64) and PaO2\<80mmHg on arterial blood gas testing\]
* Child-Pugh class A or B liver disease
* MELD score \< 20
* ≥ 18 years old
* Female subjects must be post-menopausal (defined as 12 months of spontaneous amenorrhea or 6 weeks postsurgical bilateral oophorectomy without or without hysterectomy)
* Ability to provide informed consent

Exclusion Criteria

* Enrollment in a clinical trial or concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 28 days of baseline
* Current hepatic encephalopathy
* Expectation of liver transplant within six months of randomization
* Concomitant lung disease defined as restriction (TLC \< 70%) or obstruction (FEV1 \< 80% \& FEV1/FVC \< 70%)
* Inability to comply with the study protocol
* Osteoporosis
* Premenopausal women (those who have not reached 1 year absence of menarche)
* Vulnerable study population, including imprisoned individuals, or those who cannot consent on their own.

Primary outcomes:
measure: Alveolar-Arterial Oxygen
timeFrame: 6 months
Secondary outcomes:
measure: Hormone Levels
timeFrame: 6 months
measure: Oxygen Saturation
timeFrame: 3 and 6 months
measure: Side Effects
timeFrame: 6 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Hilary M DuBrock, MD
role: PRINCIPAL_INVESTIGATOR
References: