Letrozole in Patients With Hepatopulmonary Syndrome

• Sponsor: Mayo Clinic (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04577001
• Collaborator: University of California, San Francisco (Other)
• Enrollment: 20
• Locations: 2
• Arms: 2
• Anticipated Duration (Months): 47.2
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

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
Hepatopulmonary Syndrome	Drug: Letrozole; Drug: Placebo	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: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Hilary M. DuBrock,, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04577001
• 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: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hepatopulmonary Syndrome; Syndrome; Letrozole

Study Results

No Results Posted as of Mar 24, 2022