- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02021929
Sorafenib for Hepatopulmonary Syndrome (SHPS)
Sorafenib in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Arizona
-
Phoenix, Arizona, United States, 85054
- Mayo Clinic Arizona
-
-
Illinois
-
Chicago, Illinois, United States, 60611
- Northwestern University Feinberg School of Medicine
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic - Rochester
-
-
New York
-
New York, New York, United States, 10032
- Columbia University-NewYork-Presbyterian Hospital
-
-
Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania - Perelman Center
-
-
South Carolina
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Charleston, South Carolina, United States, 29424
- Medical University of South Carolina
-
-
Texas
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Houston, Texas, United States, 77030
- University of Texas Health Science Center at Houston Medical School
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Diagnosis of HPS:
- AaPO2 ≥ 15 mm Hg (≥ 20 mm Hg for age > 64 yrs)
- Intrapulmonary shunting
- Absence of significant restriction (TLC < 70%) or obstruction (FEV1 < 80% & FEV1/FVC < 70%)
- 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:
- Active coronary artery disease
- 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:
- Single lesion ≤ 3 cm documented by LIRADS criteria
- Complete response to ablative therapy (TACE, RFA, alcohol ablation) using the modified RECIST criteria one month after therapy with no more than two treatments
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Sorafenib
400 mg (2 capsules) taken by mouth once a day
|
Sorafenib is a kinase inhibitor indicated for the treatment of:
Other Names:
|
PLACEBO_COMPARATOR: Placebo
2 capsules taken by mouth once a day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups
Time Frame: Baseline to 12 weeks
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.
Time Frame: 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
|
Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)
Time Frame: Baseline to 12 weeks
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 819185
- UM1HL116886 (NIH)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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