Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension
- Conditions
- Portopulmonary HypertensionPulmonary HypertensionCirrhosis, Liver
- Interventions
- Registration Number
- NCT03309592
- Lead Sponsor
- Ochsner Health System
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Combination Therapy Ambrisentan Pill Qualifying participants will begin combination therapy with ambrisentan pill 5 mg daily and tadalafil pill 20 mg. After one week of therapy, patients will increase tadalafil pill to 40 mg daily and continue ambrisentan pill 5 mg daily. On day 15, patients will increase ambrisentan pill to 10 mg daily and continue at 40 mg of tadalafil pill daily. Combination Therapy Tadalafil Pill Qualifying participants will begin combination therapy with ambrisentan pill 5 mg daily and tadalafil pill 20 mg. After one week of therapy, patients will increase tadalafil pill to 40 mg daily and continue ambrisentan pill 5 mg daily. On day 15, patients will increase ambrisentan pill to 10 mg daily and continue at 40 mg of tadalafil pill daily.
- Primary Outcome Measures
Name Time Method Reduction in mPAP to 35mmHg 2 months post initiation of therapy A Right Heart Catheterization will be performed in order to see if there's a reduction in mPAP to less than 35mmHg from baseline
- Secondary Outcome Measures
Name Time Method Post-Transplant Survival Outcome: Alive or Dead at 30 days Post-op Day 1 and 30 Post-transplant survival comparing subjects with or without history of POPH
Liver Function test measured by AST (iu/L) baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant AST will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver
Right Ventricular (RV) Function in centimeters Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant Tricuspid Annular Plane Systolic Excursion (TAPSE) measured in centimeters
Biomarker of Right ventricular failure baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant serum BNP
New York Heart Association Functional class baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant NYHA FC will be assessed by clinician at baseline and each subsequent visit
Blood Pressure 2 months post therapy Systemic Blood pressure
mPAP Reduction 2 months post initiation of therapy Percent reduction in mPAP will be assessed and measured from baseline via RHC
Kidney function evaluation through measurement of Creatinine levels (mg/dL) baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant Comprehensive metabolic panel will be completed at 2 months post therapy to assess kidney function
Liver Function test measured by ALT (iu/L) baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant ALT test will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver
Liver Function test measured by Bilirubin (mg/dL) baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant Bilirubin test will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver
Liver Function test measured by INR baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant INR test will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver
Right Ventricular (RV) Size in centimeters Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant To measure Right Ventricular Size in centimeters
Right Ventricular (RV) Qualitative Systolic Function: assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant To measure Right Ventricular Qualitative Systolic Function assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed
Change in 6 Minute Walk Distance baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant 6 Minute walk will be performed at baseline and each study visit
Trial Locations
- Locations (1)
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States