- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03309592
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
Status
Withdrawn
Intervention / Treatment
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
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Louisiana
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New Orleans, Louisiana, United States, 70121
- Ochsner Clinic Foundation
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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.
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Will be administered as stated in Arm/Group Descriptions
Other Names:
Will be administered as stated in Arm/Group Descriptions
Other Names:
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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
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A Right Heart Catheterization will be performed in order to see if there's a reduction in mPAP to less than 35mmHg from baseline
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2 months post initiation of therapy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood Pressure
Time Frame: 2 months post therapy
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Systemic Blood pressure
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2 months post therapy
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mPAP Reduction
Time Frame: 2 months post initiation of therapy
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Percent reduction in mPAP will be assessed and measured from baseline via RHC
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2 months post initiation of therapy
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Post-Transplant Survival Outcome: Alive or Dead at 30 days
Time Frame: Post-op Day 1 and 30
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Post-transplant survival comparing subjects with or without history of POPH
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Post-op Day 1 and 30
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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
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Comprehensive metabolic panel will be completed at 2 months post therapy to assess kidney function
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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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
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AST will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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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
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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
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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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
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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
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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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
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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
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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Right Ventricular (RV) Size in centimeters
Time Frame: Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
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To measure Right Ventricular Size in centimeters
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Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
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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
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To measure Right Ventricular Qualitative Systolic Function assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed
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Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
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Right Ventricular (RV) Function in centimeters
Time Frame: Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant
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Tricuspid Annular Plane Systolic Excursion (TAPSE) measured in centimeters
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Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant
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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
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serum BNP
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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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
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NYHA FC will be assessed by clinician at baseline and each subsequent visit
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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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
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6 Minute walk will be performed at baseline and each study visit
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baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Liver Diseases
- Fibrosis
- Hypertension
- Liver Cirrhosis
- Hypertension, Pulmonary
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Tadalafil
- Ambrisentan
Other Study ID Numbers
- ESCALATE-PPH
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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