Congenital Heart Disease, Eisenmenger's Syndrome, Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, Congenital Heart Disease, Eisenmenger's Syndrome, Prostacyclin, Iloprost
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.
Interventions
DRUGIloprost
Aerosolized iloprost, 5 mcg/dose x 6 doses daily for 3 months
Sponsors
Actelion
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 3 months | Number of Participants with adverse events, specifically mortality and heart failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Capacity | 3 months | Change in exercise duration (modified Bruce protocol), maximal oxygen consumption (VO2 max), and/or VE/VCO2 ratio. |
| Serum Brain Natriuretic Peptide (BNP) | 3 months | Change in serum BNP level |
| Quality of Life | 3 months | Change in quality of life as assessed by SF-36 QOL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iloprost Participants will be administered iloprost at 5 mcg/dose x 6 doses daily for 3 months.
Iloprost: Aerosolized iloprost, 5 mcg/dose x 6 doses daily for 3 months | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Iloprost |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Safety and Tolerability
Number of Participants with adverse events, specifically mortality and heart failure.
Time frame: 3 months
Population: Number of adverse events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iloprost | Safety and Tolerability | 0 participants |
Secondary
Exercise Capacity
Change in exercise duration (modified Bruce protocol), maximal oxygen consumption (VO2 max), and/or VE/VCO2 ratio.
Time frame: 3 months
Population: unable to analyze because study was terminated prematurely and therefore follow up assessments were not obtained
Secondary
Quality of Life
Change in quality of life as assessed by SF-36 QOL
Time frame: 3 months
Population: unable to analyze because study was terminated prematurely and therefore follow up assessments were not obtained
Secondary
Serum Brain Natriuretic Peptide (BNP)
Change in serum BNP level
Time frame: 3 months
Population: unable to analyze because study was terminated prematurely and therefore follow up assessments were not obtained