Efficacy of Remodulin in Adults With Congenital Heart Disease (ACHD) and Pulmonary Hypertension

Congenital Heart Disease Clinical Trial

Official title:

Efficacy of Remodulin in Adults With Congenital Heart Disease (ACHD) and Pulmonary Hypertension

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01980979
• Other study ID #: Remodulin in ACHD
• Secondary ID: IRB#12-001968
• Status: Withdrawn
• Phase: N/A
• First received: September 24, 2013
• Last updated: September 19, 2017
• Start date: November 2013
• Est. completion date: December 2015

Study information

• Verified date: September 2017
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of Remodulin in the treatment of adult patients with congenital heart disease and pulmonary hypertension. Baseline and post-treatment cardiopulmonary exercise tests will be performed.

Description:

A prospective, open-label, non-randomized multi-center study is proposed to assess the efficacy of Remodulin in adults with congenital heart disease and pulmonary hypertension. Subjects will be enrolled at UCLA and Ohio State University (PI: Curt Daniels, MD). The study will involve a six month trial of continuous subcutaneous Remodulin therapy, with assessments conducted prior to initiation of therapy and at 1 and 6 months following initiation of therapy. A separate initiation visit will be scheduled after the baseline visit in order to provide subjects with comprehensive training in the use and care of the Remodulin drug delivery system.

Baseline and post-treatment (6 month) assessments will include a history and physical examination, cardiopulmonary exercise test, six minute walking distance, serum brain natriuretic peptide (BNP), a Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) quality of life survey, and subjective assessment of functional capacity (New York Heart Association (NYHA) scale). The interim (1 month) follow-up visit will include a thorough review of adverse events associated with Remodulin therapy, functional class assessment, six minute walk distance, and serum BNP.

Remodulin will be initiated at 1.25 ng/kg/min and increased by 2-6 ng/kg/min weekly to a target dose of 40 ng/kg/min. If the initial infusion rate cannot be tolerated it will be reduced to 0.625 ng/kg/min. Changes in drug dose will be at the discretion of the investigators following review of interim events. If necessary, the dose may be decreased by 2 ng/kg/min every two days as tolerated.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Congenital heart disease with Pulmonary Arterial (PA) hypertension (repaired or unrepaired) defined as a mean resting directly measured Pulmonary Artery Pressure (PAP) of =35 mm Hg and/or doppler echo estimated PA systolic pressure = 60 mm Hg.

• Patients already on phosphodiesterase type 5 inhibitor (PDE-5), Endothelin Receptor Antagonist (ERA), or inhaled prostacyclin are not excluded

Exclusion Criteria:

• Age < 18 years

• Current intravenous or subcutaneous prostacyclin therapy

• Resting systemic hypotension (Systolic blood pressure < 80 mm Hg)

• Women who are pregnant or may become pregnant (unwilling to utilize effective contraception), as well as nursing mothers

• Inability to ambulate

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases
• Hypertension
• Hypertension, Pulmonary

Intervention

Drug:
• Remodulin
Subcutaneous (SQ) remodulin will be initiated at 1.25 ng/kg/min, and increased by 2-6 ng/kg/min weekly to a target dose of 40 ng/kg/min. If the initial infusion rate cannot be tolerated it will be reduced to 0.625 ng/kg/min. If subjects cannot tolerate the SQ therapy, we will attempt to switch to IV therapy.

Locations

Country	Name	City	State
United States	Ohio State University/Nationwide Children's Hospital	Columbus	Ohio
United States	UCLA Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	United Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (4)

Barst RJ, Galie N, Naeije R, Simonneau G, Jeffs R, Arneson C, Rubin LJ. Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur Respir J. 2006 Dec;28(6):1195-203. Epub 2006 Aug 9. — View Citation

Gomberg-Maitland M, Tapson VF, Benza RL, McLaughlin VV, Krichman A, Widlitz AC, Barst RJ. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1586-9. Epub 2005 Sep 8. — View Citation

Simonneau G, Barst RJ, Galie N, Naeije R, Rich S, Bourge RC, Keogh A, Oudiz R, Frost A, Blackburn SD, Crow JW, Rubin LJ; Treprostinil Study Group. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002 Mar 15;165(6):800-4. — View Citation

Tapson VF, Gomberg-Maitland M, McLaughlin VV, Benza RL, Widlitz AC, Krichman A, Barst RJ. Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest. 2006 Mar;129(3):683-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improved cardiopulmonary exercise test	Change in 6 minute walk distance after 6 months of escalating Subcutaneous (SQ) remodulin as compared to baseline.	6 months
Secondary	Improved overall cardiopulmonary variables	Change in exercise duration (modified Bruce protocol); Change in maximal oxygen consumption (VO2 max); Change in minute ventilation- carbon dioxide production (VE/VCO2) ratio; Change in serum Brain Natriuretic Peptide (BNP) level; Change in quality of life as assessed by the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) survey; Change in resting oxygen saturation; Tricuspid Annular Plane Systolic Excursion (TAPSE); Heart rate recovery	1-6 months

External Links

•   Ohio State University
•   UCLA Adult Congenital Heart Disease Center