Hepatopulmonary Syndrome
Conditions
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.
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.
Interventions
DRUGLetrozole
2.5 mg orally daily for 6 months
DRUGPlacebo
No active ingredient taken orally daily for 6 months
Sponsors
University of California, San Francisco
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
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 * 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, or those who cannot consent on their own.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alveolar-Arterial Oxygen | 6 months | To determine whether letrozole affects alveolar-arterial oxygen gradient (AaPO2) at 6 months in patients with HPS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hormone Levels | 6 months | To determine whether letrozole affects estradiol, progesterone, testosterone levels at 6 months |
| 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 |
| Side Effects | 6 months | To determine the safety and adverse effects associated with letrozole administration in patients with HPS |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Letrozole Group Subjects with hepatopulmonary syndrome will get the study drug letrozole
Letrozole: 2.5 mg orally daily for 6 months | 0 |
| Placebo Group Subjects with hepatopulmonary syndrome will get the study placebo
Placebo: No active ingredient taken orally daily for 6 months | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Subject became ineligible | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Group | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 1 |
| other Total, other adverse events | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
Primary
Alveolar-Arterial Oxygen
To determine whether letrozole affects alveolar-arterial oxygen gradient (AaPO2) at 6 months in patients with HPS.
Time frame: 6 months
Population: Study terminated due to low recruitment numbers. Data was not collected on the one enrolled participant for this outcome measure due to withdrawal after becoming ineligible prior to outcome measure timeframe completion.
Secondary
Hormone Levels
To determine whether letrozole affects estradiol, progesterone, testosterone levels at 6 months
Time frame: 6 months
Population: Study terminated due to low recruitment numbers. Data was not collected on the one enrolled participant for this outcome measure due to withdrawal after becoming ineligible prior to outcome measure timeframe completion.
Secondary
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
Time frame: 3 and 6 months
Population: Study terminated due to low recruitment numbers. Data was not collected on the one enrolled participant for this outcome measure due to withdrawal after becoming ineligible prior to outcome measure timeframe completion.
Secondary
Side Effects
To determine the safety and adverse effects associated with letrozole administration in patients with HPS
Time frame: 6 months
Population: Study terminated due to low recruitment numbers. Data was not collected on the one enrolled participant for this outcome measure due to withdrawal after becoming ineligible prior to outcome measure timeframe completion.