Sorafenib for Hepatopulmonary Syndrome

Hepatopulmonary Syndrome Clinical Trial

— SHPS  

Official title:

Sorafenib in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02021929
• Other study ID #: 819185
• Secondary ID: UM1HL116886
• Status: Terminated
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: January 2018

Study information

• Verified date: April 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this clinical trial is to determine the safety and effects of the study drug, sorafenib, in adults diagnosed with hepatopulmonary syndrome (HPS). The study will evaluate how well the drug is tolerated and its effect on the level of oxygen in the blood and the function of the lung vessels.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatopulmonary Syndrome
• Syndrome

Intervention

Drug:
• Sorafenib
Sorafenib is a kinase inhibitor indicated for the treatment of: Unresectable hepatocellular carcinoma Advanced renal cell carcinoma Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment
• Placebo

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University of Texas Health Science Center at Houston Medical School	Houston	Texas
United States	Columbia University-NewYork-Presbyterian Hospital	New York	New York
United States	University of Pennsylvania - Perelman Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic - Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups	Alveolar-arterial oxygen gradient is a calculated measure of oxygenation. It is the difference between the amount of the oxygen in the alveoli and the amount of oxygen in arterial blood.; Calculation is based on values from an Arterial Blood Gas test. Difference in change in alveolar-arterial oxygen gradient between sorafenib and placebo from baseline to 12 weeks.	Baseline to 12 weeks
Secondary	Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.	Intrapulmonary shunting is measured based on results from a saline-bubble echo test.; Number of participants with measured improvement in intrapulmonary shunting from baseline to 12 weeks in the sorafenib and placebo groups	Baseline to 12 weeks
Secondary	Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)	Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs) are obtained and measured from blood samples collected from each participant.; Difference in change from baseline to 12 weeks in the Percentage of Progenitor Cells between sorafenib and placebo groups.	Baseline to 12 weeks