Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension

Pulmonary Arterial Hypertension Clinical Trial

Official title:

Combined Clinical and Surgical Approaches to Congenital Heart Disease Associated With Pulmonary Arterial Hypertension (PAH-CHD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01548950
• Other study ID #: CAPPesq 0502/11
• Status: Completed
• Phase: N/A
• Start date: September 2011
• Est. completion date: March 2020

Study information

• Verified date: June 2015
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2020
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months and older

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Heart Disease
• Familial Primary Pulmonary Hypertension
• Heart Defects, Congenital
• Heart Diseases
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

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.

Locations

Country	Name	City	State
Brazil	Instituto do Coração (InCor) HCFMUSP	São Paulo

Sponsors (3)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	Fundação de Amparo à Pesquisa do Estado de São Paulo, Instituto do Coracao

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immediate postoperative right cardiac failure and mortality, and prevalence of residual PAH six months after surgery.	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).	Six months following surgery
Secondary	Pulmonary vascular resistance six months after surgical repair of congenital cardiac shunts with PAH	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.	Six months following surgery