Letrozole in Patients With Hepatopulmonary Syndrome

The purpose of this study is to assess the safety, tolerability and possible benefit of letrozole compared to placebo in patients with Hepatopulmonary Syndrome.

Study Overview

• Status: Recruiting
• Conditions: Hepatopulmonary Syndrome
• Intervention / Treatment: Drug: Letrozole; Drug: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jackie Reiter; Phone Number: (507) 538-2224; Email: Reiter.Jacqulyn@mayo.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco
      • Contact: Yvonne Kelly, M.D; Email: Yvonne.Kelly@ucsf.edu
      • Principal Investigator: Yvonne Kelly, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Recruiting
      • Mayo Clinic
      • Contact: Jackie R Reiter; Phone Number: 507-538-2224; Email: Reiter.Jacqulyn@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: University of California, San Francisco
• Investigators: Principal Investigator: Hilary M DuBrock, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 6, 2020

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease; Liver Diseases; Syndrome; Hepatopulmonary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: 19-005779

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No