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

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.

Study Overview

• Status: Withdrawn
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Drug: Remodulin

Detailed 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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Ohio State University/Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: treprostinil, tyvaso

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: United Therapeutics
• Investigators: Principal Investigator: Jamil A Aboulhosn, MD, UCLA Health System

Publications and helpful links

General Publications

• 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. doi: 10.1164/rccm.200505-766OC. Epub 2005 Sep 8.
• 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. doi: 10.1183/09031936.06.00044406. Epub 2006 Aug 9.
• 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. doi: 10.1378/chest.129.3.683.
• 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. doi: 10.1164/ajrccm.165.6.2106079.

Helpful Links

• UCLA Adult Congenital Heart Disease Center

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (Estimate): November 11, 2013

Study Record Updates

• Last Update Posted (Actual): September 21, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: congenital heart disease,pulmonary hypertension,prostacyclin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Hypertension; Hypertension, Pulmonary; Heart Defects, Congenital; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: Remodulin in ACHD; IRB#12-001968 (Other Identifier: IRB#12-001968)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No