Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension
The purpose of this study is to test the hypothesis that treating PAH-CHD patients preoperatively with PAH drugs and keeping them on treatment for six months after surgery reduces the risk of immediate postoperative death and the risk of residual PAH at six months following operation to <10%.
Congenital Heart Disease
Pulmonary Arterial Hypertension
Drug: Sildenafil singly or in association with Bosentan
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Combined Clinical and Surgical Approaches to Congenital Heart Disease Associated With Pulmonary Arterial Hypertension (PAH-CHD)|
- Immediate postoperative right cardiac failure and mortality, and prevalence of residual PAH six months after surgery. [ Time Frame: Six months following surgery ] [ Designated as safety issue: No ]Drug treatment must reduce the prevalence of immediate postoperative right cardiac failure / death to <10%, and the prevalence of residual PAH six months after cardiac surgery to <10%. Residual PAH is defined as an elevation of mean pulmonary artery pressure above 25 mmHg, and elevation of pulmonary vascular resistance above 3.0 Wood units x squared meters (body surface area).
- Pulmonary vascular resistance six months after surgical repair of congenital cardiac shunts with PAH [ Time Frame: Six months following surgery ] [ Designated as safety issue: No ]Drug treatment before surgery and maintained for six months following repair of congenital cardiac shunts must promote a statistically significant reduction in pulmonary vascular resistance (at six months) compared with baseline (preoperative) level.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Preoperatively, sildenafil until development of pulmonary congestion (1-4 weeks). On treatment pulmonary congestion (dyspnea and need for increasing diuretics) occurs when there is a substantial decrease in pulmonary vascular resistance, which may be confirmed noninvasively by Doppler-echocardiography. At that moment, patient will be assigned to surgery. If pulmonary congestion is not observed, bosentan will be added on top of sildenafil, and the patient will be kept on treatment for 10-12 months. In this case, a new cardiac catheterization will be performed before surgery. In both cases (short-term and medium-term treatment) patients will be kept on treatment for six months following surgery, and then re-catheterized.
Drug: Sildenafil singly or in association with Bosentan
Sildenafil, 1-4 mg/Kg/day (6-hour intervals) preoperatively, until development of pulmonary congestion (generally 1-4 weeks) or preoperatively, for 10-12 months, in association with bosentan (15.6-62.5 mg b.i.d.) if pulmonary congestion does not develop. Surgery will be performed at 1-4 weeks (short-term treatment) or at 10-12 months (medium-term treatment) if operability criteria are met (catheterization). In both cases (short and medium-term treatments), the drug or drugs will be kept for 6 months postoperatively, when final catheterization will be performed for efficacy testing.
Pulmonary arterial hypertension (PAH) is a complicating factor in the management of congenital heart disease (CHD) with intracardiac or extracardiac communications. In children with moderate to severe PAH, the risk of serious complications following the surgical repair of shunts (including right cardiac failure and death) is 15-20% or even higher, and the risk of late, postoperative residual PAH is ~25%. We therefore intend to conduct a study aimed at reducing the risk of severe immediate postoperative complications and the risk of residual PAH at six months following surgery to less than 10% in children with moderate PAH (primary objective). The study is also aimed at promoting a statistically significant reduction in pulmonary artery pressure and pulmonary vascular resistance at six month after surgery, compared with baseline in children with moderate or severe PAH (secondary objective). We hypothesized that these goals could be achieved by treating patients preoperatively and for six months postoperatively with sildenafil, either singly or combined with bosentan. Both drugs have been approved for treatment of PAH on the basis of randomized clinical trials. Preoperative and postoperative (on treatment) hemodynamic evaluation will be based on noninvasive and invasive diagnostic procedures. As an additional objective, we intend to analyze possible abnormalities in genes that have been shown to be associated with PAH-CHD, and inflammatory mediators as well. The idea is to investigate whether changes in these markers correlate with the clinical profile and response to treatments.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01548950
|Contact: Antonio Augusto B. Lopes, M.D.||55-11-2661-5000 ext email@example.com|
|Contact: Roseli Polo, Assistant||55-11-2661-5000 ext firstname.lastname@example.org|
|Instituto do Coração (InCor) HCFMUSP||Recruiting|
|São Paulo, Brazil, 05403-900|
|Contact: Antonio Augusto Lopes, M.D. 55-11-2661-5000 ext 5350 email@example.com|
|Contact: Roseli Polo, Assistant 55-11-2661-5000 ext 5350 firstname.lastname@example.org|
|Sub-Investigator: Ana Maria Thomaz, M.D.|
|Sub-Investigator: Nair Y. Maeda, PhD|
|Sub-Investigator: Vera D. Aiello, M.D.|
|Sub-Investigator: Luiz J. Kajita, M.D.|
|Sub-Investigator: Filomena Regina BG Galas, M.D.|
|Sub-Investigator: Leína Zorzanelli, M.D.|
|Sub-Investigator: Arlindo A. Riso, M.D.|
|Sub-Investigator: Marcelo B. Jatene, M.D.|
|Sub-Investigator: Sérgio P. Bydlowski, M.D.|
|Principal Investigator:||Antonio Augusto Lopes, M.D.||Instituto do Coração (InCor) - HCFMUSP - São Paulo - Brazil|