Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension

December 5, 2018 updated by: Ochsner Health System

Investigator Sponsored Research Proposal : Efficacy and Safety of Combination Ambrisentan and TadaLafil in PATiEnts With PortoPulmonary Hypertension (ESCALATE-PPH)

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.

Study Overview

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.

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Combination Therapy
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.
Will be administered as stated in Arm/Group Descriptions
Other Names:
  • Letairis
Will be administered as stated in Arm/Group Descriptions
Other Names:
  • Adcirca

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction in mPAP to 35mmHg
Time Frame: 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
2 months post initiation of therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Pressure
Time Frame: 2 months post therapy
Systemic Blood pressure
2 months post therapy
mPAP Reduction
Time Frame: 2 months post initiation of therapy
Percent reduction in mPAP will be assessed and measured from baseline via RHC
2 months post initiation of therapy
Post-Transplant Survival Outcome: Alive or Dead at 30 days
Time Frame: Post-op Day 1 and 30
Post-transplant survival comparing subjects with or without history of POPH
Post-op Day 1 and 30
Kidney function evaluation through measurement of Creatinine levels (mg/dL)
Time Frame: 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
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Liver Function test measured by AST (iu/L)
Time Frame: 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
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Liver Function test measured by ALT (iu/L)
Time Frame: 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
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Liver Function test measured by Bilirubin (mg/dL)
Time Frame: 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
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Liver Function test measured by INR
Time Frame: 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
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Right Ventricular (RV) Size in centimeters
Time Frame: Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
To measure Right Ventricular Size in centimeters
Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
Right Ventricular (RV) Qualitative Systolic Function: assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed
Time Frame: 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
Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
Right Ventricular (RV) Function in centimeters
Time Frame: Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant
Tricuspid Annular Plane Systolic Excursion (TAPSE) measured in centimeters
Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant
Biomarker of Right ventricular failure
Time Frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
serum BNP
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
New York Heart Association Functional class
Time Frame: 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
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Change in 6 Minute Walk Distance
Time Frame: 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
baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Stacy Mandras, MD, Director, Pulmonary Hypertension

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 12, 2017

Primary Completion (ACTUAL)

November 1, 2018

Study Completion (ACTUAL)

November 1, 2018

Study Registration Dates

First Submitted

June 5, 2017

First Submitted That Met QC Criteria

October 9, 2017

First Posted (ACTUAL)

October 13, 2017

Study Record Updates

Last Update Posted (ACTUAL)

December 7, 2018

Last Update Submitted That Met QC Criteria

December 5, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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