Portopulmonary HypertensionPhase 4NCT03309592
Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension
A Phase 4 study testing Ambrisentan Pill and Tadalafil Pill in people with Portopulmonary Hypertension and Pulmonary Hypertension, run by Ochsner Health System at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Portopulmonary Hypertension, Pulmonary Hypertension, Cirrhosis, Liver
- What is being tested?
- Ambrisentan Pill and Tadalafil Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Oct 2017to 1 Nov 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
About this study
Official title: 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.
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.
- Being tested
- Ambrisentan Pill, Tadalafil Pill
- Medical subject headings
- Hypertension, Pulmonary, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ambrisentan PillDrug
Also called Letairis
Will be administered as stated in Arm/Group Descriptions
Tadalafil PillDrug
Also called Adcirca
Will be administered as stated in Arm/Group Descriptions
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Other | 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. Receives: Drug: Ambrisentan Pill; Drug: Tadalafil Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 months post initiation of therapy
Secondary outcomes (14)
Blood Pressure
Systemic Blood pressure
Measured: 2 months post therapy
mPAP Reduction
Percent reduction in mPAP will be assessed and measured from baseline via RHC
Measured: 2 months post initiation of therapy
Post-Transplant Survival Outcome: Alive or Dead at 30 days
Post-transplant survival comparing subjects with or without history of POPH
Measured: Post-op Day 1 and 30
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
Measured: 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)
AST will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver
Measured: 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)
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
Measured: 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)
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
Measured: 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
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
Measured: 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
To measure Right Ventricular Size in centimeters
Measured: 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
To measure Right Ventricular Qualitative Systolic Function assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed
Measured: Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
Right Ventricular (RV) Function in centimeters
Tricuspid Annular Plane Systolic Excursion (TAPSE) measured in centimeters
Measured: Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant
Biomarker of Right ventricular failure
serum BNP
Measured: 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
NYHA FC will be assessed by clinician at baseline and each subsequent visit
Measured: 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
6 Minute walk will be performed at baseline and each study visit
Measured: baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2017
- Study start12 Oct 2017
- Primary completion1 Nov 2018
- Study completion1 Nov 2018
Why it stopped: Lack of eligible participants and failure to meeting study enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Portopulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ochsner Health System
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Stacy Mandras, MD, Principal investigator, Director, Pulmonary Hypertension
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03309592
- Sponsor's protocol ID
- ESCALATE-PPH
- Status last verified
- Dec 2018
- First submitted
- 5 Jun 2017
- Last updated
- 7 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigator Sponsored Research Proposal : Efficacy and Safety of Combination Ambrisentan and TadaLafil in PATiEnts With PortoPulmonary Hypertension (ESCALATE-PPH)
- ClinicalTrials.gov ID
- NCT03309592
- Acronym / sponsor ID
- ESCALATE-PPH
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of eligible participants and failure to meeting study enrollment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ochsner Health SystemUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- 12 Oct 2017 (actual)
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 13 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Other | Drug: Ambrisentan Pill, Drug: Tadalafil PillQualifying 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ambrisentan PillAlso: LetairisWill be administered as stated in Arm/Group Descriptions | Drug | Combination Therapy |
| Tadalafil PillAlso: AdcircaWill be administered as stated in Arm/Group Descriptions | Drug | Combination Therapy |
Primary outcome
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
14 secondary outcomes
Blood Pressure
Time frame: 2 months post therapy
mPAP Reduction
Time frame: 2 months post initiation of therapy
Post-Transplant Survival Outcome: Alive or Dead at 30 days
Time frame: 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
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
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
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
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
Right Ventricular (RV) Size in centimeters
Time frame: 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
Right Ventricular (RV) Function in centimeters
Time frame: 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
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
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2018.
- Individual participant dataSharing planned: No
Related trials for Portopulmonary Hypertension
Not yet recruitingObservational study
Heart Problems in Children With Chronic Liver Disease
Chronic Liver Disease (CLD), Liver Cirrhosis
Not yet recruitingObservational study
Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension
Portopulmonary Hypertension, Pulmonary Arterial Hypertension (PAH)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stacy Mandras, MD principal investigator
Director, Pulmonary Hypertension
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ambrisentan Pill and Tadalafil Pill in people with Portopulmonary Hypertension and Pulmonary Hypertension, run by Ochsner Health System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in mPAP to 35mmHg (time frame: 2 months post initiation of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2018.