Iloprost for the Treatment of Pulmonary Hypertension in Adults With Congenital Heart Disease

NCT01319045 | Terminated Results

• 1 other identifier: Iloprost ACHD
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary arterial hypertension (PAH), or high blood pressure in the lungs, is common in patients with congenital heart disease. Historically these patients suffered significant morbidity and mortality due to a lack of effective therapies. More recently, advanced therapies which target the mechanisms underlying the development and progression of PAH have been introduced into clinical care. Oral, intravenous, subcutaneous, and inhaled therapies are all available for the treatment of PAH. Patients with PAH are first treated with oral agents (including sildenafil and bosentan). However, if these agents fail to achieve the desired effect for the patient, intravenous or inhaled therapies may be initiated. Combination therapy with multiple agents is common in routine clinical care. However, the most efficacious therapeutic regimen has yet to be delineated. The present study seeks to evaluate the efficacy of one specific regimen: iloprost, an inhaled prostacyclin derivative, used in combination with oral therapy (sildenafil and/or bosentan). Iloprost has been approved by the FDA for use in this patient population. Adults with PAH already receiving oral therapy will be invited to participate in this study. Iloprost will be added to their current therapeutic regimen for a period of three months, with pre- and post-treatment assessments. These will include a cardiopulmonary exercise test, BNP (a blood test), six minute walking distance, and a quality of life questionnaire.

Conditions

Pulmonary Arterial Hypertension; Congenital Heart Disease; Eisenmenger's Syndrome

Keywords

Pulmonary Arterial Hypertension; Congenital Heart Disease; Eisenmenger's Syndrome; Prostacyclin; Iloprost

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  Number of Participants with adverse events, specifically mortality and heart failure.

  3 months

Secondary Outcomes (3)

• Exercise Capacity

  3 months

• Serum Brain Natriuretic Peptide (BNP)

  3 months

• Quality of Life

  3 months

Study Arms (1)

Iloprost

EXPERIMENTAL

Participants will be administered iloprost at 5 mcg/dose x 6 doses daily for 3 months.

Drug: Iloprost

Interventions

Iloprost DRUG

Aerosolized iloprost, 5 mcg/dose x 6 doses daily for 3 months

Also known as: Ventavis, prostacyclin analogue

Iloprost

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years old
• Congenital heart disease with pulmonary arterial hypertension and cyanosis (resting oxygen saturation \< 90% on room air)
• Stable on oral therapy (PDE5 inhibitor and/or endothelin blockade) for at least three months

You may not qualify if:

• Age \< 18 years old
• Current intravenous or subcutaneous prostacyclin therapy
• Resting Systemic Hypotension (Systolic blood pressure \< 85 mmHg)
• Women who are pregnant or may become pregnant (unwilling to utilize effective contraception), as well as nursing mothers
• Inability to ambulate
• Planned surgical procedure during the study period

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Actelion: collaborator

Study Sites (1)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Related Publications (13)

• Beghetti M, Tissot C. Pulmonary arterial hypertension in congenital heart diseases. Semin Respir Crit Care Med. 2009 Aug;30(4):421-8. doi: 10.1055/s-0029-1233311. Epub 2009 Jul 24.

  PMID: 19634081 BACKGROUND

• Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):13S-24S. doi: 10.1016/j.jacc.2004.02.029.

  PMID: 15194174 BACKGROUND

• Niwa K, Perloff JK, Kaplan S, Child JS, Miner PD. Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart. J Am Coll Cardiol. 1999 Jul;34(1):223-32. doi: 10.1016/s0735-1097(99)00153-9.

  PMID: 10400015 BACKGROUND

• Daliento L, Somerville J, Presbitero P, Menti L, Brach-Prever S, Rizzoli G, Stone S. Eisenmenger syndrome. Factors relating to deterioration and death. Eur Heart J. 1998 Dec;19(12):1845-55. doi: 10.1053/euhj.1998.1046.

  PMID: 9886728 BACKGROUND

• Christman BW. Lipid mediator dysregulation in primary pulmonary hypertension. Chest. 1998 Sep;114(3 Suppl):205S-207S. doi: 10.1378/chest.114.3_supplement.205s.

  PMID: 9741570 BACKGROUND

• Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH, Koerner SK, Langleben D, Keller CA, Murali S, Uretsky BF, Clayton LM, Jobsis MM, Blackburn SD, Shortino D, Crow JW; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996 Feb 1;334(5):296-301. doi: 10.1056/NEJM199602013340504.

  PMID: 8532025 BACKGROUND

• Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, Rich S, Barst RJ, Barrett PS, Kral KM, Jobsis MM, Loyd JE, Murali S, Frost A, Girgis R, Bourge RC, Ralph DD, Elliott CG, Hill NS, Langleben D, Schilz RJ, McLaughlin VV, Robbins IM, Groves BM, Shapiro S, Medsger TA Jr. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med. 2000 Mar 21;132(6):425-34. doi: 10.7326/0003-4819-132-6-200003210-00002.

  PMID: 10733441 BACKGROUND

• 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.

  PMID: 11897647 BACKGROUND

• Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper MM, Behr J, Winkler J, Sitbon O, Popov W, Ghofrani HA, Manes A, Kiely DG, Ewert R, Meyer A, Corris PA, Delcroix M, Gomez-Sanchez M, Siedentop H, Seeger W; Aerosolized Iloprost Randomized Study Group. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002 Aug 1;347(5):322-9. doi: 10.1056/NEJMoa020204.

  PMID: 12151469 BACKGROUND

• McLaughlin VV, Oudiz RJ, Frost A, Tapson VF, Murali S, Channick RN, Badesch DB, Barst RJ, Hsu HH, Rubin LJ. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006 Dec 1;174(11):1257-63. doi: 10.1164/rccm.200603-358OC. Epub 2006 Aug 31.

  PMID: 16946127 BACKGROUND

• Krug S, Sablotzki A, Hammerschmidt S, Wirtz H, Seyfarth HJ. Inhaled iloprost for the control of pulmonary hypertension. Vasc Health Risk Manag. 2009;5(1):465-74. doi: 10.2147/vhrm.s3223.

  PMID: 19475782 BACKGROUND

• Hallioglu O, Dilber E, Celiker A. Comparison of acute hemodynamic effects of aerosolized and intravenous iloprost in secondary pulmonary hypertension in children with congenital heart disease. Am J Cardiol. 2003 Oct 15;92(8):1007-9. doi: 10.1016/s0002-9149(03)00991-3.

  PMID: 14556887 BACKGROUND

• Limsuwan A, Khosithseth A, Wanichkul S, Khowsathit P. Aerosolized iloprost for pulmonary vasoreactivity testing in children with long-standing pulmonary hypertension related to congenital heart disease. Catheter Cardiovasc Interv. 2009 Jan 1;73(1):98-104. doi: 10.1002/ccd.21793.

  PMID: 19089967 BACKGROUND

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Heart Defects, Congenital; Eisenmenger Complex

Interventions

Iloprost

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Limitations and Caveats

Enrollment was too slow. The trial was discontinued.

Results Point of Contact

• Title: Jamil Aboulhosn
• Organization: UCLA

jaboulhosn@mednet.ucla.edu

310-825-5950

Study Officials

• Jamil A Aboulhosn, MD

  Ahmanson / UCLA Adult Congenital Heart Disease Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 18, 2011
• First Posted: March 21, 2011
• Study Start: June 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 26, 2015
• Results First Posted: December 29, 2014

Record last verified: 2015-01

Locations

US (1)