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Sorafenib for Hepatopulmonary Syndrome (SHPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hepatopulmonary Syndrome
Interventions Drug: Sorafenib
Drug: Placebo
Enrollment 28
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description

400 mg (2 capsules) taken by mouth once a day

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

2 capsules taken by mouth once a day

Placebo

Period Title: Overall Study
Started 16 12
Completed 14 11
Not Completed 2 1
Arm/Group Title Sorafenib Placebo Total
Hide Arm/Group Description

400 mg (2 capsules) taken by mouth once a day

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

2 capsules taken by mouth once a day

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 16 12 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 16 participants 12 participants 28 participants
60
(53 to 64)
59
(54 to 63)
60
(53 to 64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 12 participants 28 participants
Female
10
  62.5%
6
  50.0%
16
  57.1%
Male
6
  37.5%
6
  50.0%
12
  42.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 12 participants 28 participants
Hispanic or Latino
1
   6.3%
4
  33.3%
5
  17.9%
Not Hispanic or Latino
15
  93.8%
8
  66.7%
23
  82.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 12 participants 28 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
16
 100.0%
10
  83.3%
26
  92.9%
More than one race
0
   0.0%
2
  16.7%
2
   7.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants 12 participants 28 participants
16 12 28
World Health Organization functional class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 12 participants 28 participants
Class I
3
  18.8%
4
  33.3%
7
  25.0%
Class II
6
  37.5%
2
  16.7%
8
  28.6%
Class III
7
  43.8%
6
  50.0%
13
  46.4%
[1]
Measure Description:

Classification based on evaluation of the participant.

Class I: Patients without limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near-syncope.

Class II: Patients with slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near-syncope.

Class III: Patients with marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes undue dyspnea or fatigue, chest pain or near-syncope.

Childs-Pugh Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 12 participants 28 participants
A
7
  43.8%
3
  25.0%
10
  35.7%
B
9
  56.3%
9
  75.0%
18
  64.3%
[1]
Measure Description: Child-Pugh Class consists of five clinical features and is used to assess the prognosis of chronic liver disease and cirrhosis. There are three distinct classes of increasing severity (A, B and C). Class is determined based on a score that accounts for five factors: total bilirubin level, serum albumin, INR, degree of ascites, and degree of hepatic encephalopathy.
Model for End-stage Liver Disease   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 12 participants 28 participants
13
(11 to 14)
13
(10 to 15)
13
(10 to 15)
[1]
Measure Description:

A numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates. It gives each person a number based on how urgently he or she needs a liver transplant within the next three months. The number is calculated by a formula using three routine lab test results:

  • bilirubin, which measures how effectively the liver excretes bile;
  • INR (prothrombin time), which measures the liver’s ability to make blood clotting factors; and
  • creatinine, which measures kidney function. (Impaired kidney function is often associated with severe liver disease.)
1.Primary Outcome
Title Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups
Hide Description

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.

Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description:

400 mg (2 capsules) taken by mouth once a day

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

2 capsules taken by mouth once a day

Placebo

Overall Number of Participants Analyzed 14 11
Median (Inter-Quartile Range)
Unit of Measure: mm Hg
4.5
(-3.8 to 7.0)
-2.4
(-4.8 to 8.2)
2.Secondary Outcome
Title Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.
Hide Description

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

Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Since all of the participants did not complete the 12 week study visit, data from fewer participants were available to be analyzed in each arm for this measure.
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description:

400 mg (2 capsules) taken by mouth once a day

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

2 capsules taken by mouth once a day

Placebo

Overall Number of Participants Analyzed 12 9
Measure Type: Count of Participants
Unit of Measure: Participants
3
  25.0%
6
  66.7%
3.Secondary Outcome
Title Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)
Hide Description

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.

Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Since all of the participants did not complete the 12 week study visit, data from fewer participants were available to be analyzed in each arm for this measure.
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description:

400 mg (2 capsules) taken by mouth once a day

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

2 capsules taken by mouth once a day

Placebo

Overall Number of Participants Analyzed 12 10
Median (Inter-Quartile Range)
Unit of Measure: percentage of PBMCs
0.01
(-0.02 to 0.04)
0.04
(0.00 to 0.07)
Time Frame 14 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description

400 mg (2 capsules) taken by mouth once a day

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

2 capsules taken by mouth once a day

Placebo

All-Cause Mortality
Sorafenib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/16 (6.25%)   0/12 (0.00%) 
Hide Serious Adverse Events
Sorafenib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   7/16 (43.75%)   5/12 (41.67%) 
Blood and lymphatic system disorders     
Platelet count low  1  0/16 (0.00%)  1/12 (8.33%) 
General disorders     
Diagnostic procedure  1  1/16 (6.25%)  0/12 (0.00%) 
Hepatobiliary disorders     
Encephalopathy  1  2/16 (12.50%)  0/12 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/16 (6.25%)  1/12 (8.33%) 
Psychiatric disorders     
Mania  1  0/16 (0.00%)  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders     
Hypoxia  1  1/16 (6.25%)  0/12 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin infection (Fournier's gangrene)  1  1/16 (6.25%)  0/12 (0.00%) 
Surgical and medical procedures     
Liver transplant  1  1/16 (6.25%)  2/12 (16.67%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sorafenib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   16/16 (100.00%)   12/12 (100.00%) 
Cardiac disorders     
Hypertension  1  3/16 (18.75%)  2/12 (16.67%) 
Edema  1  2/16 (12.50%)  1/12 (8.33%) 
Gastrointestinal disorders     
Diarrhea  1  5/16 (31.25%)  4/12 (33.33%) 
Abdominal pain  1  2/16 (12.50%)  5/12 (41.67%) 
Nausea  1  3/16 (18.75%)  3/12 (25.00%) 
General disorders     
Weight loss  1  5/16 (31.25%)  2/12 (16.67%) 
Fatigue  1  3/16 (18.75%)  3/12 (25.00%) 
Pruritus  1  3/16 (18.75%)  3/12 (25.00%) 
Headache  1  4/16 (25.00%)  0/12 (0.00%) 
Myalgia  1  2/16 (12.50%)  2/12 (16.67%) 
Alopecia  1  2/16 (12.50%)  1/12 (8.33%) 
Mucositis (oral)  1  3/16 (18.75%)  0/12 (0.00%) 
Nasal congestion  1  1/16 (6.25%)  2/12 (16.67%) 
Pain in extremity  1  2/16 (12.50%)  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  2/16 (12.50%)  3/12 (25.00%) 
Upper respiratory infection  1  1/16 (6.25%)  2/12 (16.67%) 
Skin and subcutaneous tissue disorders     
Rash (maculo-papular)  1  4/16 (25.00%)  1/12 (8.33%) 
Dry skin  1  3/16 (18.75%)  0/12 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Recruitment difficult due to challenges in screening for HPS, lack of patient awareness of HPS, and hesitation from potential subjects due to sorafenib side effects. Sample size reduced and sponsor terminated trial before reaching target sample size
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Steven Kawut
Organization: University of Pennsylvania
Phone: 215-573-0258
EMail: kawut@upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02021929    
Other Study ID Numbers: 819185
UM1HL116886 ( U.S. NIH Grant/Contract )
First Submitted: December 20, 2013
First Posted: December 27, 2013
Results First Submitted: February 25, 2019
Results First Posted: April 25, 2019
Last Update Posted: April 25, 2019