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Trial record 1 of 2 for:    Ambrisentan and Tadalafil | Recruiting, Not yet recruiting, Available Studies
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Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension

This study is not yet open for participant recruitment.
Verified October 2017 by Ochsner Health System
Sponsor:
ClinicalTrials.gov Identifier:
NCT03309592
First Posted: October 13, 2017
Last Update Posted: October 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Ochsner Health System
  Purpose
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.

Condition Intervention Phase
Portopulmonary Hypertension Pulmonary Hypertension Cirrhosis, Liver Drug: Ambrisentan Pill Drug: Tadalafil Pill Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigator Sponsored Research Proposal : Efficacy and Safety of Combination Ambrisentan and TadaLafil in PATiEnts With PortoPulmonary Hypertension (ESCALATE-PPH)

Resource links provided by NLM:


Further study details as provided by Ochsner Health System:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Blood Pressure [ Time Frame: 2 months post therapy ]
    Systemic Blood pressure

  • mPAP Reduction [ Time Frame: 2 months post initiation of therapy ]
    Percent reduction in mPAP will be assessed and measured from baseline via RHC

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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


Estimated Enrollment: 20
Anticipated Study Start Date: November 2017
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Ambrisentan Pill
Will be administered as stated in Arm/Group Descriptions
Other Name: Letairis
Drug: Tadalafil Pill
Will be administered as stated in Arm/Group Descriptions
Other Name: Adcirca

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03309592


Contacts
Contact: Stacy Mandras, MD 504-842-6729 smandras@ochsner.org
Contact: Amelia Ferguson, MS 504-842-6729 amelia.ferguson@ochsner.org

Sponsors and Collaborators
Ochsner Health System
Gilead Sciences
Investigators
Principal Investigator: Stacy Mandras, MD Director, Pulmonary Hypertension
  More Information

Responsible Party: Ochsner Health System
ClinicalTrials.gov Identifier: NCT03309592     History of Changes
Other Study ID Numbers: ESCALATE-PPH
First Submitted: June 5, 2017
First Posted: October 13, 2017
Last Update Posted: October 13, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Tadalafil
Ambrisentan
Hypertension
Hypertension, Pulmonary
Liver Cirrhosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Liver Diseases
Digestive System Diseases
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Antihypertensive Agents