Clinical trial NCT01548950: Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension
Official title: Combined Clinical and Surgical Approaches to Congenital Heart Disease Associated With Pulmonary Arterial Hypertension (PAH-CHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Heart Disease
Pulmonary Arterial Hypertension
Keywords: Congenital heart disease
Pulmonary arterial hypertension
Sildenafil
Bosentan
Pediatric cardiac surgery
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Instituto do Coracao
name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2012-03-08
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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%.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Potentially operable patients with congenital cardiac septal defects (bi-ventricular physiology) and PAH, must have at least three of the following severity criteria: age \> 18 months; absence of congestive heart failure (pulmonary congestion); Down syndrome; bidirectional shunting across the septal defect; periods of systemic (peripheral) oxygen saturation \< 90%.

Exclusion Criteria:

* Patients with complex cardiac anomalies for whom there are no possibilities of complete repair. Patients with uni-ventricular physiology.

Primary outcomes:
measure: Immediate postoperative right cardiac failure and mortality, and prevalence of residual PAH six months after surgery.
timeFrame: Six months following surgery
Secondary outcomes:
measure: Pulmonary vascular resistance six months after surgical repair of congenital cardiac shunts with PAH
timeFrame: Six months following surgery
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Coração (InCor) HCFMUSP
Study officials:
affiliation: Instituto do Coração (InCor) - HCFMUSP - São Paulo - Brazil
name: Antonio Augusto Lopes, M.D.
role: PRINCIPAL_INVESTIGATOR
References: