Trial Outcomes & Findings for Sorafenib for Hepatopulmonary Syndrome (NCT NCT02021929)
NCT ID: NCT02021929
Last Updated: 2019-04-25
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
28 participants
Primary outcome timeframe
Baseline to 12 weeks
Results posted on
2019-04-25
Participant Flow
Participant milestones
| Measure |
Sorafenib
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
|
Placebo
2 capsules taken by mouth once a day
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
12
|
|
Overall Study
COMPLETED
|
14
|
11
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sorafenib for Hepatopulmonary Syndrome
Baseline characteristics by cohort
| Measure |
Sorafenib
n=16 Participants
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
|
Placebo
n=12 Participants
2 capsules taken by mouth once a day
Placebo
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
59 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
12 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
World Health Organization functional class
Class I
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
World Health Organization functional class
Class II
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
World Health Organization functional class
Class III
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Childs-Pugh Class
A
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Childs-Pugh Class
B
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Model for End-stage Liver Disease
|
13 units on a scale
n=5 Participants
|
13 units on a scale
n=7 Participants
|
13 units on a scale
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 12 weeksAlveolar-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.
Outcome measures
| Measure |
Sorafenib
n=14 Participants
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
|
Placebo
n=11 Participants
2 capsules taken by mouth once a day
Placebo
|
|---|---|---|
|
Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups
|
4.5 mm Hg
Interval -3.8 to 7.0
|
-2.4 mm Hg
Interval -4.8 to 8.2
|
SECONDARY outcome
Timeframe: Baseline to 12 weeksPopulation: 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.
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
Outcome measures
| Measure |
Sorafenib
n=12 Participants
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
|
Placebo
n=9 Participants
2 capsules taken by mouth once a day
Placebo
|
|---|---|---|
|
Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.
|
3 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline to 12 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Sorafenib
n=12 Participants
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
|
Placebo
n=10 Participants
2 capsules taken by mouth once a day
Placebo
|
|---|---|---|
|
Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)
|
0.01 percentage of PBMCs
Interval -0.02 to 0.04
|
0.04 percentage of PBMCs
Interval 0.0 to 0.07
|
Adverse Events
Sorafenib
Serious events: 7 serious events
Other events: 16 other events
Deaths: 1 deaths
Placebo
Serious events: 5 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sorafenib
n=16 participants at risk
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
|
Placebo
n=12 participants at risk
2 capsules taken by mouth once a day
Placebo
|
|---|---|---|
|
Hepatobiliary disorders
Encephalopathy
|
12.5%
2/16 • 14 weeks
|
0.00%
0/12 • 14 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
6.2%
1/16 • 14 weeks
|
8.3%
1/12 • 14 weeks
|
|
General disorders
Diagnostic procedure
|
6.2%
1/16 • 14 weeks
|
0.00%
0/12 • 14 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
6.2%
1/16 • 14 weeks
|
0.00%
0/12 • 14 weeks
|
|
Psychiatric disorders
Mania
|
0.00%
0/16 • 14 weeks
|
8.3%
1/12 • 14 weeks
|
|
Surgical and medical procedures
Liver transplant
|
6.2%
1/16 • 14 weeks
|
16.7%
2/12 • 14 weeks
|
|
Blood and lymphatic system disorders
Platelet count low
|
0.00%
0/16 • 14 weeks
|
8.3%
1/12 • 14 weeks
|
|
Skin and subcutaneous tissue disorders
Skin infection (Fournier's gangrene)
|
6.2%
1/16 • 14 weeks
|
0.00%
0/12 • 14 weeks
|
Other adverse events
| Measure |
Sorafenib
n=16 participants at risk
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
|
Placebo
n=12 participants at risk
2 capsules taken by mouth once a day
Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
31.2%
5/16 • 14 weeks
|
33.3%
4/12 • 14 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
2/16 • 14 weeks
|
41.7%
5/12 • 14 weeks
|
|
General disorders
Weight loss
|
31.2%
5/16 • 14 weeks
|
16.7%
2/12 • 14 weeks
|
|
General disorders
Fatigue
|
18.8%
3/16 • 14 weeks
|
25.0%
3/12 • 14 weeks
|
|
Gastrointestinal disorders
Nausea
|
18.8%
3/16 • 14 weeks
|
25.0%
3/12 • 14 weeks
|
|
General disorders
Pruritus
|
18.8%
3/16 • 14 weeks
|
25.0%
3/12 • 14 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
2/16 • 14 weeks
|
25.0%
3/12 • 14 weeks
|
|
Cardiac disorders
Hypertension
|
18.8%
3/16 • 14 weeks
|
16.7%
2/12 • 14 weeks
|
|
Skin and subcutaneous tissue disorders
Rash (maculo-papular)
|
25.0%
4/16 • 14 weeks
|
8.3%
1/12 • 14 weeks
|
|
General disorders
Headache
|
25.0%
4/16 • 14 weeks
|
0.00%
0/12 • 14 weeks
|
|
General disorders
Myalgia
|
12.5%
2/16 • 14 weeks
|
16.7%
2/12 • 14 weeks
|
|
General disorders
Alopecia
|
12.5%
2/16 • 14 weeks
|
8.3%
1/12 • 14 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
18.8%
3/16 • 14 weeks
|
0.00%
0/12 • 14 weeks
|
|
Cardiac disorders
Edema
|
12.5%
2/16 • 14 weeks
|
8.3%
1/12 • 14 weeks
|
|
General disorders
Mucositis (oral)
|
18.8%
3/16 • 14 weeks
|
0.00%
0/12 • 14 weeks
|
|
General disorders
Nasal congestion
|
6.2%
1/16 • 14 weeks
|
16.7%
2/12 • 14 weeks
|
|
General disorders
Pain in extremity
|
12.5%
2/16 • 14 weeks
|
8.3%
1/12 • 14 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
6.2%
1/16 • 14 weeks
|
16.7%
2/12 • 14 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place