Ascites, Liver Cirrhosis, Portal Hypertension
Conditions
Brief summary
The purpose of this study is to demonstrate that TIPS with the GORE® VIATORR® TIPS Endoprosthesis improves transplant-free survival compared to LVP alone in patients who have cirrhosis of the liver with portal hypertension and difficult to treat ascites.
Interventions
DEVICETIPS procedure with the GORE® VIATORR® TIPS Endoprosthesis
TIPS procedure with the GORE® VIATORR® TIPS Endoprosthesis
PROCEDURELVP
Large Volume Paracentesis
DEVICETIPS procedure with the GORE® VIATORR® TIPS Endoprosthesis for subjects who failed LVP and crossed over to TIPS per protocol
Sponsors
W.L.Gore & Associates
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
\> Patient has cirrhosis of the liver with portal hypertension \> Patient has difficult to treat ascites \> Patient is 18 years or older and \<70 years old at randomization \> Patient is willing and able to comply with all study protocol requirements, including specified follow-up and testing. \> Patient, or legal authorized representative, is willing to provide written informed consent prior to enrollment in the study.
Exclusion criteria
\> Patient has more than 6 large volume paracenteses within 90 days prior to randomization \> Patient is contraindicated for TIPS placement \> Patient has had previous TIPS placement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transplant-free Survival | Through 24 months | Time from randomization to death from any cause prior to transplant. Subjects who undergo liver transplant will be censored at the time of transplant. Subjects without an event will be censored at the date of last follow-up. * Note: The outcome entered below is the number of participants who were either alive or had a liver transplant at time of study termination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Transplant | Through 24 months | Time from randomization to transplant. Subjects without an event will be censored at the date of last follow-up or date of death without transplant. \*Note: Outcome measure entered is number of subjects who received a liver transplant at time of study termination. |
| Frequency of Paracentesis | Through 24 months | Number of paracentesis post randomization |
| Overall Survival | Through 24 months | Time from randomization to death from any cause. Subjects without an event will be censored at the date of last follow-up. \> \*Note: Outcome measure entered below is number of subjects alive at time of study termination. |
| Procedural Success | Time of TIPS Procedure (within 2 weeks of enrollment for TIPS arm, at least 6 months after enrollment for Control arm crossover participants) | Successful creation of a VIATORR(R) device lined portosystemic shunt spanning a hepatic vein and intrahepatic branch of the portal vein \*Note: Control (LVP) arm includes only subjects who crossed over to TIPS |
| Liver Disease Complications (Adverse Events) | Through 24 months | Overall frequency and component frequencies. Complications will include hepatic encephalopathy, hepatic hydrothorax, hepatoma, hepatorenal syndrome (Type 1 or Type 2), hyponatremia (\<130mEq / L), spontaneous bacterial peritonitis, and variceal bleeding. |
| Frequency of Hepatic Encephalopathy | Through 24 months | Number of episodes of West Haven grade 2 or greater |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TIPS TIPS with GORE® VIATORR® TIPS Endoprosthesis \>
\> TIPS procedure with the GORE® VIATORR® TIPS Endoprosthesis: TIPS procedure with the GORE® VIATORR® TIPS Endoprosthesis | 13 |
| LVP (Large Volume Paracentesis) Large Volume Paracentesis
\*A subject may be crossed-over from large volume paracentesis to TIPS with GORE® VIATORR® TIPS Endoprosthesis if the subject has completed their six month study visit and has met the criteria for cross-over (LVP failure). | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Termination of study by sponsor | 11 | 13 |
Baseline characteristics
| Characteristic | TIPS | LVP (Large Volume Paracentesis) | Total |
|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 6.6 | 57.5 years STANDARD_DEVIATION 8 | 58.0 years STANDARD_DEVIATION 7.2 |
| Region of Enrollment Canada | 2 participants | 4 participants | 6 participants |
| Region of Enrollment United States | 11 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 11 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 13 | 3 / 13 |
| serious Total, serious adverse events | 6 / 13 | 2 / 13 |
Outcome results
Primary
Transplant-free Survival
Time from randomization to death from any cause prior to transplant. Subjects who undergo liver transplant will be censored at the time of transplant. Subjects without an event will be censored at the date of last follow-up. * Note: The outcome entered below is the number of participants who were either alive or had a liver transplant at time of study termination.
Time frame: Through 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIPS | Transplant-free Survival | 11 participants |
| LVP (Large Volume Paracentesis) | Transplant-free Survival | 13 participants |
Secondary
Frequency of Hepatic Encephalopathy
Number of episodes of West Haven grade 2 or greater
Time frame: Through 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIPS | Frequency of Hepatic Encephalopathy | 4 Number of episodes |
| LVP (Large Volume Paracentesis) | Frequency of Hepatic Encephalopathy | 2 Number of episodes |
Secondary
Frequency of Paracentesis
Number of paracentesis post randomization
Time frame: Through 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIPS | Frequency of Paracentesis | 25 Number of episodes |
| LVP (Large Volume Paracentesis) | Frequency of Paracentesis | 93 Number of episodes |
Secondary
Liver Disease Complications (Adverse Events)
Overall frequency and component frequencies. Complications will include hepatic encephalopathy, hepatic hydrothorax, hepatoma, hepatorenal syndrome (Type 1 or Type 2), hyponatremia (\<130mEq / L), spontaneous bacterial peritonitis, and variceal bleeding.
Time frame: Through 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Variceal Bleeding | 0 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Hepatorenal Syndrome Type II | 0 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Hepatoma | 0 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Hyponatremia | 1 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Hepatic Hydrothorax | 2 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Spontaneous Bacterial Peritonitis | 0 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Hepatorenal Syndrome Type 1 | 0 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Subjects with Hepatic Encephalopathy | 3 participants |
| TIPS | Liver Disease Complications (Adverse Events) | Total Subjects with Liver Disease Complication | 5 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Hepatic Encephalopathy | 1 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Total Subjects with Liver Disease Complication | 4 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Variceal Bleeding | 0 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Hepatic Hydrothorax | 1 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Hepatoma | 1 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Hepatorenal Syndrome Type 1 | 0 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Hepatorenal Syndrome Type II | 1 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Hyponatremia | 1 participants |
| LVP (Large Volume Paracentesis) | Liver Disease Complications (Adverse Events) | Subjects with Spontaneous Bacterial Peritonitis | 0 participants |
Secondary
Overall Survival
Time from randomization to death from any cause. Subjects without an event will be censored at the date of last follow-up. \> \*Note: Outcome measure entered below is number of subjects alive at time of study termination.
Time frame: Through 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIPS | Overall Survival | 11 participants |
| LVP (Large Volume Paracentesis) | Overall Survival | 13 participants |
Secondary
Procedural Success
Successful creation of a VIATORR(R) device lined portosystemic shunt spanning a hepatic vein and intrahepatic branch of the portal vein \*Note: Control (LVP) arm includes only subjects who crossed over to TIPS
Time frame: Time of TIPS Procedure (within 2 weeks of enrollment for TIPS arm, at least 6 months after enrollment for Control arm crossover participants)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIPS | Procedural Success | 12 participants |
| LVP (Large Volume Paracentesis) | Procedural Success | 4 participants |
Secondary
Time to Transplant
Time from randomization to transplant. Subjects without an event will be censored at the date of last follow-up or date of death without transplant. \*Note: Outcome measure entered is number of subjects who received a liver transplant at time of study termination.
Time frame: Through 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIPS | Time to Transplant | 1 participants |
| LVP (Large Volume Paracentesis) | Time to Transplant | 1 participants |