Sorafenib for Hepatopulmonary Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02021929
• Date of registration: 20/12/2013
• Prospective Registration: Yes
• Primary sponsor: University of Pennsylvania
• Public title: Sorafenib for Hepatopulmonary Syndrome SHPS
• Scientific title: Sorafenib in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial
• Date of first enrolment: March 2014
• Target sample size: 28
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02021929
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Steven M Kawut, MD, MS
• Affiliation: University of Pennsylvania

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of HPS:

1. AaPO2 = 15 mm Hg (= 20 mm Hg for age > 64 yrs)

2. Intrapulmonary shunting

3. Absence of significant restriction (TLC < 70%) or obstruction (FEV1 < 80% &
FEV1/FVC < 70%)

4. Presence of cirrhosis/hepatic fibrosis and/or portal hypertension

- Child-Pugh class A or B liver disease

- Platelet count = 30 ×10e9 per liter

- Hemoglobin = 8.5 g per deciliter

- International normalized ratio = 2.3

- Albumin = 2.8 g per deciliter

- Total bilirubin = 5 mg per deciliter

- Alanine aminotransferase and aspartate aminotransferase = 5 times the upper limit of
the normal range

- Serum creatinine = 1.5 times the upper limit of the normal range and not receiving
dialysis

- Negative pregnancy test (for women of childbearing potential) at both screening and
baseline visits. Post-menopausal women (defined as no menses for one year) and
surgically sterilized women are not required to undergo a pregnancy test.

- Subjects (men and women) of childbearing potential must agree to use medically
acceptable contraception beginning at the signing of the Informed Consent Form until
at least 14 days after the last dose of study drug.

- Age = 21 years

- Ability to provide informed consent

Exclusion Criteria:

- Recent chronic heavy alcohol consumption

- 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
screening visit

- Current hepatic encephalopathy

- Active infection

- Diagnosis of portopulmonary hypertension

- WHO Class IV functional status

- Congenital long-QT syndrome

- Subjects who have used strong CYP3A4 inducers (e.g., phenytoin, carbamazepine,
phenobarbital, St. John's Wort [Hypericum perforatum], dexamethasone at a dose of
greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days
before randomization

- Subjects who are currently taking Coumadin®(warfarin)

- Active or clinically significant cardiac disease, including:

1. Active coronary artery disease

2. Unstable angina (anginal symptoms at rest), new-onset angina within 12 weeks
before randomization, or myocardial infarction within 24 weeks before
randomization

- Liver or other solid organ transplant recipients

- Expectation of liver transplant within four months of randomization

- Hepatocellular carcinoma that does not meet all of the following criteria:

1. Single lesion = 3 cm documented by LIRADS criteria

2. Complete response to ablative therapy (TACE, RFA, alcohol ablation) using the
modified RECIST criteria one month after therapy with no more than two treatments

3. No other lesions develop after initiation of HCC therapy

- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm
Hg on repeated measurement) despite optimal medical management.

- Any hemorrhage/bleeding event of NCI-Common Toxicity Criteria for Adverse Effects v4.0
Grade 3 or higher within 4 weeks before randomization

- Presence of a non-healing wound, non-healing ulcer, or bone fracture

- Women who are pregnant or breast-feeding

- Major surgery 28 days prior to randomization

- Subjects with any previously untreated or concurrent cancer except cervical cancer
in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects
surviving a cancer that was curatively treated and without evidence of disease for
more than 3 years before randomization are allowed. All cancer treatments
(chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor
embolization) must be completed at least 3 years prior to study entry (i.e., signature
date of the informed consent form).

- Inability to comply with the protocol and/or not willing or not available for
follow-up assessments



Age minimum: 21 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hepatopulmonary Syndrome

Intervention(s)

Drug: Placebo

Drug: Sorafenib

Primary Outcome(s)

Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups [Time Frame: Baseline to 12 weeks]

Secondary Outcome(s)

Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs) [Time Frame: Baseline to 12 weeks]

Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks. [Time Frame: Baseline to 12 weeks]

Secondary ID(s)

819185

UM1HL116886

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Heart, Lung, and Blood Institute (NHLBI)

Results

• Results available: Yes
• Date Posted: 25/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02021929