Letrozole in Patients With Hepatopulmonary Syndrome

Study Overview
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Brief Summary
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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
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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.

Official Title
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Letrozole in Patients With Hepatopulmonary Syndrome

Conditions
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Hepatopulmonary Syndrome

Intervention / Treatment
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* Drug: Letrozole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 MELD exception score > 28 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, non-English speaking patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole Group<br>Subjects with hepatopulmonary syndrome will get the study drug letrozole | Drug: Letrozole<br>* 2.5 mg orally daily for 6 months<br>|
| Placebo Comparator: Placebo Group<br>Subjects with hepatopulmonary syndrome will get the study placebo | Drug: Placebo<br>* No active ingredient taken orally daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alveolar-Arterial Oxygen | To determine whether letrozole affects alveolar-arterial oxygen gradient (AaPO2) at 6 months in patients with HPS. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hormone Levels | To determine whether letrozole affects estradiol, progesterone, testosterone levels at 6 months | 6 months | 
| Oxygen Saturation | • To determine whether letrozole affects oxygen saturation from pulse oximetry at 3 months 6 months and distance walked in 6 minutes in patients with HPS | 3 and 6 months | 
| Side effects | • To determine the safety and adverse effects associated with letrozole administration in patients with HPS | 6 months |