Letrozole in Patients With Hepatopulmonary Syndrome

Mayo Clinic (Other)
Overall Status
CT.gov ID
University of California, San Francisco (Other)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Anticipated Enrollment :
20 participants
Intervention Model:
Parallel Assignment
Double (Participant, Investigator)
Primary Purpose:
Official Title:
Letrozole in Patients With Hepatopulmonary Syndrome
Actual Study Start Date :
Jan 25, 2021
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Dec 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Letrozole Group

Subjects with hepatopulmonary syndrome will get the study drug letrozole

Drug: Letrozole
2.5 mg orally daily for 6 months

Placebo Comparator: Placebo Group

Subjects with hepatopulmonary syndrome will get the study placebo

Drug: Placebo
No active ingredient taken orally daily for 6 months

Outcome Measures

Primary Outcome Measures

  1. Alveolar-Arterial Oxygen [6 months]

    To determine whether letrozole affects alveolar-arterial oxygen gradient (AaPO2) at 6 months in patients with HPS.

Secondary Outcome Measures

  1. Hormone Levels [6 months]

    To determine whether letrozole affects estradiol, progesterone, testosterone levels at 6 months

  2. Oxygen Saturation [3 and 6 months]

    • 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. Side effects [6 months]

    • To determine the safety and adverse effects associated with letrozole administration in patients with HPS

Eligibility Criteria


Ages Eligible for Study:
18 Years to 99 Years
Sexes Eligible for Study:
Accepts Healthy Volunteers:

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

Contacts and Locations


Site City State Country Postal Code
1 University of California San Francisco San Francisco California United States 94143
2 Mayo Clinic Rochester Minnesota United States 55902

Sponsors and Collaborators

  • Mayo Clinic
  • University of California, San Francisco


  • Principal Investigator: Hilary M DuBrock, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:


None provided.
Responsible Party:
Hilary M. DuBrock,, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier:
Other Study ID Numbers:
  • 19-005779
First Posted:
Oct 6, 2020
Last Update Posted:
Mar 24, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 24, 2022