Letrozole in Patients With Hepatopulmonary Syndrome

• ClinicalTrials.gov Identifier: NCT04577001
• Recruitment Status: Recruiting
• First Posted: October 6, 2020
• Last Update Posted: February 17, 2021
• Sponsor: Mayo Clinic
• Collaborator: University of California, San Francisco
• Information provided by (Responsible Party): Hilary M. DuBrock,, Mayo Clinic

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 (Clinical Trial)
• Estimated 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: January 25, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 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 [ Time Frame: 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 [ Time Frame: 6 months ]
   To determine whether letrozole affects estradiol, progesterone, testosterone levels at 6 months
2. Oxygen Saturation [ Time Frame: 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 [ Time Frame: 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 (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
• 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

Contacts

Contact: Jackie Reiter; (507) 538-2224; Reiter.Jacqulyn@mayo.edu

Locations

United States, California

University of California San Francisco; Recruiting

San Francisco, California, United States, 94143

Contact: Yvonne Kelly, M.D Yvonne.Kelly@ucsf.edu

Principal Investigator: Yvonne Kelly, MD

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55902

Contact: Jackie R Reiter 507-538-2224 Reiter.Jacqulyn@mayo.edu

Sponsors and Collaborators

Mayo Clinic

University of California, San Francisco

Investigators

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

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Hilary M. DuBrock,, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04577001
• Other Study ID Numbers: 19-005779
• First Posted: October 6, 2020
• Last Update Posted: February 17, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• 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; Disease; Pathologic Processes; Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Letrozole; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs