Ambrisentan in Single Ventricle

NCT02080637 | Completed Phase 2 Results

• 1 other identifier: Pro00050118
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: To evaluate the pharmacokinetics, bioavailability and hemodynamic efficacy of ambrisentan after Fontan surgical palliation of single ventricle heart defects. Study activities and population group: Children undergoing Fontan surgical palliation for single ventricle defects will be eligible for the study. Up to 20 subjects will be enrolled (16 ambrisentan, 4 placebo) and will receive 3 days (3 doses) of ambrisentan starting on post-operative day #1 upon returning from the operating room. Ambrisentan plasma levels will be obtained at specified time points during treatment. Post-operative monitoring lines will be used to measure effects of ambrisentan on hemodynamics and pulmonary / systemic endothelial function.

Conditions

Hypoplastic Left Heart Syndrome; Hypoplastic Right-sided Heart Complex

Keywords

Single ventricle

Outcome Measures

Primary Outcomes (2)

• Area Under the Curve for Ambrisentan Plasma Concentration

  Plasma samples collected at 0-1,1-6,18-30 and 40-60 hours after administration of the first ambrisentan dose.

  0-1,1-6,18-30 and 40-60 hours

• Change in Pulmonary Vascular Resistance Index

  Hemodynamic data, including Fontan pressures, common atrial pressures and saturations, will be collected at the specified timepoints. Pressures and saturations will be measured from existing monitoring lines. Standard Fick calculations will be used to calculate pulmonary vascular resistance (calculated as trans-pulmonary gradient \[Fontan pressure - atrial pressure\] / pulmonary blood flow \[Qp\]) and reported in Wood Units x m\^2.

  baseline to 2 hours post ambrisentan administration

Secondary Outcomes (2)

• Amount of Chest Tube Drainage Post Fontan Operation

  0-96 hours post Fontan

• Duration of Chest Tube Drainage Post Fontan Operation

  measured for the duration of the post-operative hospitalization or for 30 days, whichever is shorter

Study Arms (2)

Ambrisentan

ACTIVE COMPARATOR

Oral ambrisentan 2.5 - 5 mg, single dose, once daily

Drug: Ambrisentan

Placebo

PLACEBO COMPARATOR

Oral placebo 2.5 - 5 mg, single dose, once daily

Other: Placebo

Interventions

Ambrisentan DRUG

Once daily oral dosing

Also known as: Leitaris

Ambrisentan

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 24 Months - 120 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥ 24 months; ≤120 months.
• History of congenital heart disease with severe hypoplasia of a right or left ventricle.
• Undergoing Fontan surgery as part of standard clinical care.
• Availability and willingness of the parent/legally authorized representative to provide written informed consent and, as appropriate, assent from the child.

You may not qualify if:

• History of serious adverse event related to ambrisentan administration.
• History of ambrisentan exposure within 48 hours of the study.
• Presence of pulmonary venous obstruction.
• Treatment with cyclosporin.
• Any of the following - as determined by the attending physician
• Significant hemodynamic instability
• Sepsis.
• Need for ECMO support.
• Renal failure defined as serum creatinine \> 2 times higher than the upper limit of normal.
• Liver dysfunction defined as alanine aminotransferase or aspartate aminotransferase \> 3 times higher than the upper limit of normal.
• Thrombocytopenia defined as a platelet count \< 50 000 cells/µL.
• Leukopenia defined as white blood cells \< 2500 cells/µL.
• Anemia defined as hemoglobin \< 8mg/dL.
• Atrial hypertension (mean LA pressure \> 12mm Hg).

Sponsors & Collaborators

• Kevin Hill: lead

Study Sites (1)

Duke Universtiy Hospital

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Hypoplastic Left Heart Syndrome; Baetz-Greenwalt syndrome; Univentricular Heart

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Kevin Hill, M.D.
• Organization: Duke University

kevin.hill@duke.edu

919-668-8305

Study Officials

• Kevin Hill, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assist Professor

Study Record Dates

• First Submitted: February 21, 2014
• First Posted: March 6, 2014
• Study Start: July 1, 2015
• Primary Completion: July 20, 2017
• Study Completion: August 20, 2017
• Last Updated: September 12, 2019
• Results First Posted: September 12, 2019

Record last verified: 2019-08

Locations

US (1)