CClinicalTrials.gg
WithdrawnNCT03309592Updated Dec 7, 2018

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

A Phase 4 interventional study of Ambrisentan Pill and Tadalafil Pill in Portopulmonary Hypertension, Pulmonary Hypertension and Cirrhosis, Liver, sponsored by Ochsner Health System. Withdrawn at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-12-07.

Sponsored by Ochsner Health System · Phase 4, Interventional, and Treatment

Why this study was withdrawn
Lack of eligible participants and failure to meeting study enrollment.
Phase
Phase 4
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Portopulmonary Hypertension
  • Pulmonary Hypertension
  • Cirrhosis, Liver
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • 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.

    Drug: Ambrisentan Pill · Drug: Tadalafil Pill

Interventions

  • DrugAmbrisentan Pill

    Will be administered as stated in Arm/Group Descriptions

    Also known as: Letairis

  • DrugTadalafil Pill

    Will be administered as stated in Arm/Group Descriptions

    Also known as: Adcirca

05

What researchers measure

Primary outcomes

  1. Reduction in mPAP to 35mmHg

    A Right Heart Catheterization will be performed in order to see if there's a reduction in mPAP to less than 35mmHg from baseline

    Time frame: 2 months post initiation of therapy

Secondary outcomes

  1. Blood Pressure

    Systemic Blood pressure

    Time frame: 2 months post therapy

  2. mPAP Reduction

    Percent reduction in mPAP will be assessed and measured from baseline via RHC

    Time frame: 2 months post initiation of therapy

  3. Post-Transplant Survival Outcome: Alive or Dead at 30 days

    Post-transplant survival comparing subjects with or without history of POPH

    Time frame: Post-op Day 1 and 30

  4. Kidney function evaluation through measurement of Creatinine levels (mg/dL)

    Comprehensive metabolic panel will be completed at 2 months post therapy to assess kidney function

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

  5. Liver Function test measured by AST (iu/L)

    AST will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

  6. Liver Function test measured by ALT (iu/L)

    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

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

  7. Liver Function test measured by Bilirubin (mg/dL)

    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

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

  8. Liver Function test measured by INR

    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

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

  9. Right Ventricular (RV) Size in centimeters

    To measure Right Ventricular Size in centimeters

    Time frame: Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant

  10. Right Ventricular (RV) Qualitative Systolic Function: assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed

    To measure Right Ventricular 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

  11. Right Ventricular (RV) Function in centimeters

    Tricuspid Annular Plane Systolic Excursion (TAPSE) measured in centimeters

    Time frame: Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant

  12. Biomarker of Right ventricular failure

    serum BNP

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

  13. New York Heart Association Functional class

    NYHA FC will be assessed by clinician at baseline and each subsequent visit

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

  14. Change in 6 Minute Walk Distance

    6 Minute walk will be performed at baseline and each study visit

    Time frame: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant

06

Study locations

1 site
  • Ochsner Clinic Foundation
    New Orleans, Louisiana 70121, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03309592
Lead sponsor
Ochsner Health System
Collaborators
Gilead Sciences
Responsible party
Sponsor
First posted
Oct 13, 2017
Start date
Oct 12, 2017
Primary completion
Nov 1, 2018
Completion
Nov 1, 2018
Last update
Dec 7, 2018

Study contacts

Stacy Mandras, MD
principal investigator · Director, Pulmonary Hypertension

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Dec 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion