Clinical trial NCT03309592: Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension
Official title: Investigator Sponsored Research Proposal : Efficacy and Safety of Combination Ambrisentan and TadaLafil in PATiEnts With PortoPulmonary Hypertension (ESCALATE-PPH)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Portopulmonary Hypertension
Pulmonary Hypertension
Cirrhosis, Liver
Lead sponsor: Ochsner Health System
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2017-10-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of the combination of ambrisentan and tadalafil in reducing mPAP to below 35mmHg in patients with moderate to severe Portopulmonary Hypertension (POPH) as a means to candidacy for liver transplantation.

Detailed description: The outcome of liver transplantation (LT) in the presence of moderate to severe POPH is significantly poor with a 50% reported mortality rate in LT recipients having a mean pulmonary artery pressure (mPAP) \>35 mmHg and 100% when the mPAP is greater than 50 mmHg; therefore, making moderate to severe POPH a contraindication to liver transplants. Those recipients with significant pulmonary artery pressure (PAP) may be denied the opportunity for transplant unless the mPAP is brought below 35 mmHg with medical treatment. This study will test the efficacy \& safety of the combination of using ambrisentan and tadalfil in reducing the Pulmonary Arterial Pressure to below 35 mmHg in patients with moderate to severe POPH as a means to candidacy for liver transplantation.

Eligibility criteria: Inclusion Criteria:

* Child-Pugh Class Class A \& B Cirrhosis
* mPAP ≥35mmHg
* Pulmonary Capillary Wedge Pressure (PWCP) \<15mmHg on Right Heart Catheterization's (RHCs)
* mPAP \> 50mmHg will be considered eligible unless they are World Health Organization (WHO) Functional Class IV

Exclusion Criteria:

* End stage renal disease on hemodialysis (ESRD on HD)
* Renal dysfunction and GFR \< 30
* AST, ALT \> 5 times the upper limit of normal
* Total bilirubin ≥ 6.0
* INR \> 2

  * Initially, Child-Pugh Class C patients will be excluded; however, after the first 5 patients are included, if there is no signal of worsening liver function, the protocol may be amended to include patients with Class C cirrhosis.

Primary outcomes:
measure: Reduction in mPAP to 35mmHg
timeFrame: 2 months post initiation of therapy
Secondary outcomes:
measure: Blood Pressure
timeFrame: 2 months post therapy
measure: mPAP Reduction
timeFrame: 2 months post initiation of therapy
measure: Post-Transplant Survival Outcome: Alive or Dead at 30 days
timeFrame: Post-op Day 1 and 30
measure: Kidney function evaluation through measurement of Creatinine levels (mg/dL)
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
measure: Liver Function test measured by AST (iu/L)
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
measure: Liver Function test measured by ALT (iu/L)
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
measure: Liver Function test measured by Bilirubin (mg/dL)
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
measure: Liver Function test measured by INR
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
measure: Right Ventricular (RV) Size in centimeters
timeFrame: Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
measure: Right Ventricular (RV) Qualitative Systolic Function: assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed
timeFrame: Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
measure: Right Ventricular (RV) Function in centimeters
timeFrame: Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant
measure: Biomarker of Right ventricular failure
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
measure: New York Heart Association Functional class
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
measure: Change in 6 Minute Walk Distance
timeFrame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
Study officials:
affiliation: Director, Pulmonary Hypertension
name: Stacy Mandras, MD
role: PRINCIPAL_INVESTIGATOR
References: