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Sorafenib for Hepatopulmonary Syndrome (SHPS)

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ClinicalTrials.gov Identifier: NCT02021929
Recruitment Status : Terminated
First Posted : December 27, 2013
Results First Posted : April 25, 2019
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE December 20, 2013
First Posted Date  ICMJE December 27, 2013
Results First Submitted Date  ICMJE February 25, 2019
Results First Posted Date  ICMJE April 25, 2019
Last Update Posted Date April 25, 2019
Study Start Date  ICMJE March 2014
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
Difference in changes in AaPO2 between sorafenib and placebo groups [ Time Frame: 12 weeks ]
measured by Arterial Blood Gas testing
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
  • Difference in changes in intrapulmonary shunting between sorafenib and placebo groups [ Time Frame: 12 weeks ]
  • Difference in changes in HPC and other biomarker levels between sorafenib and placebo groups [ Time Frame: 6 weeks ]
  • Difference in changes in HPC and other biomarker levels between sorafenib and placebo groups [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sorafenib for Hepatopulmonary Syndrome
Official Title  ICMJE Sorafenib in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hepatopulmonary Syndrome
Intervention  ICMJE
  • 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
    Other Name: Nexavar
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Sorafenib
    400 mg (2 capsules) taken by mouth once a day
    Intervention: Drug: Sorafenib
  • Placebo Comparator: Placebo
    2 capsules taken by mouth once a day
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 14, 2018)
28
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2013)
50
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02021929
Other Study ID Numbers  ICMJE 819185
UM1HL116886 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Steven M Kawut, MD, MS University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP