Ignite Creation Date:
2025-12-24 @ 3:43 PM
Ignite Modification Date:
2026-02-01 @ 9:24 PM
Study NCT ID:
NCT03309592
Status:
WITHDRAWN
Last Update Posted:
2018-12-07
First Post:
2017-06-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006976', 'term': 'Hypertension, Pulmonary'}, {'id': 'D008103', 'term': 'Liver Cirrhosis'}], 'ancestors': [{'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D006973', 'term': 'Hypertension'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005355', 'term': 'Fibrosis'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C467894', 'term': 'ambrisentan'}, {'id': 'D000068581', 'term': 'Tadalafil'}], 'ancestors': [{'id': 'D002243', 'term': 'Carbolines'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D026121', 'term': 'Indole Alkaloids'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006575', 'term': 'Heterocyclic Compounds, 3-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Lack of eligible participants and failure to meeting study enrollment.', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2017-10-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-12', 'completionDateStruct': {'date': '2018-11-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-12-05', 'studyFirstSubmitDate': '2017-06-05', 'studyFirstSubmitQcDate': '2017-10-09', 'lastUpdatePostDateStruct': {'date': '2018-12-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-10-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-11-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Reduction in mPAP to 35mmHg', 'timeFrame': '2 months post initiation of therapy', 'description': "A Right Heart Catheterization will be performed in order to see if there's a reduction in mPAP to less than 35mmHg from baseline"}], 'secondaryOutcomes': [{'measure': 'Blood Pressure', 'timeFrame': '2 months post therapy', 'description': 'Systemic Blood pressure'}, {'measure': 'mPAP Reduction', 'timeFrame': '2 months post initiation of therapy', 'description': 'Percent reduction in mPAP will be assessed and measured from baseline via RHC'}, {'measure': 'Post-Transplant Survival Outcome: Alive or Dead at 30 days', 'timeFrame': 'Post-op Day 1 and 30', 'description': 'Post-transplant survival comparing subjects with or without history of POPH'}, {'measure': 'Kidney function evaluation through measurement of Creatinine levels (mg/dL)', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': 'Comprehensive metabolic panel will be completed at 2 months post therapy to assess kidney function'}, {'measure': 'Liver Function test measured by AST (iu/L)', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': 'AST will be done to monitor and measure the degree of cirrhosis on the liver as well as the overall function of the liver'}, {'measure': 'Liver Function test measured by ALT (iu/L)', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': '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'}, {'measure': 'Liver Function test measured by Bilirubin (mg/dL)', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': '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'}, {'measure': 'Liver Function test measured by INR', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': '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'}, {'measure': 'Right Ventricular (RV) Size in centimeters', 'timeFrame': 'Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant', 'description': 'To measure Right Ventricular Size in centimeters'}, {'measure': 'Right Ventricular (RV) Qualitative Systolic Function: assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed', 'timeFrame': 'Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant', 'description': 'To measure Right Ventricular Qualitative Systolic Function assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed'}, {'measure': 'Right Ventricular (RV) Function in centimeters', 'timeFrame': 'Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant', 'description': 'Tricuspid Annular Plane Systolic Excursion (TAPSE) measured in centimeters'}, {'measure': 'Biomarker of Right ventricular failure', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': 'serum BNP'}, {'measure': 'New York Heart Association Functional class', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': 'NYHA FC will be assessed by clinician at baseline and each subsequent visit'}, {'measure': 'Change in 6 Minute Walk Distance', 'timeFrame': 'baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant', 'description': '6 Minute walk will be performed at baseline and each study visit'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Portopulmonary Hypertension', 'Pulmonary Hypertension', 'Cirrhosis, Liver']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Child-Pugh Class Class A \\& B Cirrhosis\n* mPAP ≥35mmHg\n* Pulmonary Capillary Wedge Pressure (PWCP) \\<15mmHg on Right Heart Catheterization's (RHCs)\n* mPAP \\> 50mmHg will be considered eligible unless they are World Health Organization (WHO) Functional Class IV\n\nExclusion Criteria:\n\n* End stage renal disease on hemodialysis (ESRD on HD)\n* Renal dysfunction and GFR \\< 30\n* AST, ALT \\> 5 times the upper limit of normal\n* Total bilirubin ≥ 6.0\n* INR \\> 2\n\n * 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."}, 'identificationModule': {'nctId': 'NCT03309592', 'briefTitle': 'Efficacy and Safety of Combination Ambrisentan and Tadalafil in Patients With Portopulmonary Hypertension', 'organization': {'class': 'OTHER', 'fullName': 'Ochsner Health System'}, 'officialTitle': 'Investigator Sponsored Research Proposal : Efficacy and Safety of Combination Ambrisentan and TadaLafil in PATiEnts With PortoPulmonary Hypertension (ESCALATE-PPH)', 'orgStudyIdInfo': {'id': 'ESCALATE-PPH'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Combination Therapy', 'description': '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.', 'interventionNames': ['Drug: Ambrisentan Pill', 'Drug: Tadalafil Pill']}], 'interventions': [{'name': 'Ambrisentan Pill', 'type': 'DRUG', 'otherNames': ['Letairis'], 'description': 'Will be administered as stated in Arm/Group Descriptions', 'armGroupLabels': ['Combination Therapy']}, {'name': 'Tadalafil Pill', 'type': 'DRUG', 'otherNames': ['Adcirca'], 'description': 'Will be administered as stated in Arm/Group Descriptions', 'armGroupLabels': ['Combination Therapy']}]}, 'contactsLocationsModule': {'locations': [{'zip': '70121', 'city': 'New Orleans', 'state': 'Louisiana', 'country': 'United States', 'facility': 'Ochsner Clinic Foundation', 'geoPoint': {'lat': 29.95465, 'lon': -90.07507}}], 'overallOfficials': [{'name': 'Stacy Mandras, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Director, Pulmonary Hypertension'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Ochsner Health System', 'class': 'OTHER'}, 'collaborators': [{'name': 'Gilead Sciences', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}