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

Pulmonary Arterial Hypertension Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01319045
• Other study ID #: Iloprost ACHD
• Status: Terminated
• Phase: N/A
• First received: March 18, 2011
• Last updated: January 13, 2015
• Start date: June 2011
• Est. completion date: May 2013

Study information

• Verified date: January 2015
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congenital Heart Disease
• Eisenmenger Complex
• Eisenmenger's Syndrome
• Heart Defects, Congenital
• Heart Diseases
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Iloprost
Aerosolized iloprost, 5 mcg/dose x 6 doses daily for 3 months

Locations

Country	Name	City	State
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	Actelion

Country where clinical trial is conducted

United States, 

References & Publications (13)

Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, Rich S, Barst RJ, Barrett PS, Kral KM, Jöbsis 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. — View Citation

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, Jöbsis 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. — View Citation

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. Review. — View Citation

Christman BW. Lipid mediator dysregulation in primary pulmonary hypertension. Chest. 1998 Sep;114(3 Suppl):205S-207S. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. Epub 2006 Aug 31. — View Citation

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. — View Citation

Olschewski H, Simonneau G, Galiè 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. — 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

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability	Number of Participants with adverse events, specifically mortality and heart failure.	3 months	Yes
Secondary	Exercise Capacity	Change in exercise duration (modified Bruce protocol), maximal oxygen consumption (VO2 max), and/or VE/VCO2 ratio.	3 months	No
Secondary	Serum Brain Natriuretic Peptide (BNP)	Change in serum BNP level	3 months	No
Secondary	Quality of Life	Change in quality of life as assessed by SF-36 QOL	3 months	No