Hepatopulmonary SyndromePhase 2SHPSNCT02021929
Sorafenib for Hepatopulmonary Syndrome
A Phase 2 study testing Sorafenib in people with Hepatopulmonary Syndrome, run by University of Pennsylvania at 7 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Hepatopulmonary Syndrome
- What is being tested?
- Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 7 sitesUnited States
- Study dates
- Mar 2014to Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Medical University of South Carolina
Charleston, South Carolina, 29424
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
University of Texas Health Science Center at Houston Medical School
Houston, Texas, 77030
Columbia University-NewYork-Presbyterian Hospital
New York, New York, 10032
University of Pennsylvania - Perelman Center
Philadelphia, Pennsylvania, 19104
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
About this study
Official title: Sorafenib in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial
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.
- Conditions
- Hepatopulmonary Syndrome
- Being tested
- Sorafenib, Placebo
- Keywords
- Randomized Controlled Trial, Clinical Trial, sorafenib, Hepatopulmonary Syndrome
- Medical subject headings
- Hepatopulmonary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called Nexavar
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
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib | Experimental | 400 mg (2 capsules) taken by mouth once a day Receives: Drug: Sorafenib |
| Placebo | Placebo comparator | 2 capsules taken by mouth once a day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 12 weeks
Secondary outcomes (2)
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
Measured: Baseline to 12 weeks
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.
Measured: Baseline to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2013 (estimated)
- Study startMar 2014
- Primary completionJan 2018
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatopulmonary SyndromeStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Steven M Kawut, MD, MS, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02021929
- Sponsor's protocol ID
- 819185
- Other IDs
- UM1HL116886
- Acronym
- SHPS
- Status last verified
- Apr 2019
- First submitted
- 20 Dec 2013
- Last updated
- 25 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sorafenib in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02021929
- Acronym / sponsor ID
- SHPS / 819185
- Conditions
- Hepatopulmonary Syndrome
- Keywords
- Randomized Controlled Trial, Clinical Trial, sorafenib, Hepatopulmonary Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2014
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 27 Dec 2013 (estimated)
- Results
- Posted 25 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sorafenib | Experimental | Drug: Sorafenib400 mg (2 capsules) taken by mouth once a day |
| Placebo | Placebo comparator | Drug: Placebo2 capsules taken by mouth once a day |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Diagnosis of HPS:
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibAlso: NexavarSorafenib 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 | Drug | Sorafenib |
| Placebo | Drug | Placebo |
Primary outcome
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.
2 secondary outcomes
Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.
Time frame: Baseline to 12 weeks
Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)
Time frame: Baseline to 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
Related trials for Hepatopulmonary Syndrome
Enrolling by invitationObservational study
International Registry of Congenital Portosystemic Shunt (IRCPSS)
Congenital Portosystemic Shunt, CPSS (Congenital Portosystemic Shunt)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven M Kawut, MD, MS principal investigator
University of Pennsylvania
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib in people with Hepatopulmonary Syndrome, run by University of Pennsylvania at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups (time frame: Baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2019.