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

Pulmonary Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03309592
• Other study ID #: ESCALATE-PPH
• Status: Withdrawn
• Phase: Phase 4
• Start date: October 12, 2017
• Est. completion date: November 1, 2018

Study information

• Verified date: December 2018
• Source: Ochsner Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 1, 2018
• Est. primary completion date: November 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Hypertension
• Hypertension, Pulmonary
• Liver Cirrhosis
• Portopulmonary Hypertension
• Pulmonary Hypertension

Intervention

Drug:
• Ambrisentan Pill
Will be administered as stated in Arm/Group Descriptions
• Tadalafil Pill
Will be administered as stated in Arm/Group Descriptions

Locations

Country	Name	City	State
United States	Ochsner Clinic Foundation	New Orleans	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Ochsner Health System	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 months post initiation of therapy
Secondary	Blood Pressure	Systemic Blood pressure	2 months post therapy
Secondary	mPAP Reduction	Percent reduction in mPAP will be assessed and measured from baseline via RHC	2 months post initiation of therapy
Secondary	Post-Transplant Survival Outcome: Alive or Dead at 30 days	Post-transplant survival comparing subjects with or without history of POPH	Post-op Day 1 and 30
Secondary	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	baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Secondary	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	baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Secondary	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	baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Secondary	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	baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Secondary	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	baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Secondary	Right Ventricular (RV) Size in centimeters	To measure Right Ventricular Size in centimeters	Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
Secondary	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	Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant
Secondary	Right Ventricular (RV) Function in centimeters	Tricuspid Annular Plane Systolic Excursion (TAPSE) measured in centimeters	Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant
Secondary	Biomarker of Right ventricular failure	serum BNP	baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant
Secondary	New York Heart Association Functional class	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
Secondary	Change in 6 Minute Walk Distance	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