Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2012 by University of Sao Paulo General Hospital
Sponsor:
Collaborators:
Instituto do Coracao
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT01548950
First received: March 5, 2012
Last updated: January 9, 2014
Last verified: March 2012
  Purpose

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%.


Condition Intervention
Congenital Heart Disease
Pulmonary Arterial Hypertension
Drug: Sildenafil singly or in association with Bosentan

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo General Hospital:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 50
Study Start Date: September 2011
Estimated Study Completion Date: December 2015
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Single-arm study
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.

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

Ages Eligible for Study:   2 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01548950

Contacts
Contact: Antonio Augusto B. Lopes, M.D. 55-11-2661-5000 ext 5350 aablopes@usp.br
Contact: Roseli Polo, Assistant 55-11-2661-5000 ext 5350 roseli.polo@incor.usp.br

Locations
Brazil
Instituto do Coração (InCor) HCFMUSP Recruiting
São Paulo, Brazil, 05403-900
Contact: Antonio Augusto Lopes, M.D.    55-11-2661-5000 ext 5350    aablopes@usp.br   
Contact: Roseli Polo, Assistant    55-11-2661-5000 ext 5350    roseli.polo@incor.usp.br   
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.         
Sponsors and Collaborators
University of Sao Paulo General Hospital
Instituto do Coracao
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Antonio Augusto Lopes, M.D. Instituto do Coração (InCor) - HCFMUSP - São Paulo - Brazil
  More Information

No publications provided

Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT01548950     History of Changes
Other Study ID Numbers: CAPPesq 0502/11
Study First Received: March 5, 2012
Last Updated: January 9, 2014
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo General Hospital:
Congenital heart disease
Pulmonary arterial hypertension
Sildenafil
Bosentan
Pediatric cardiac surgery

Additional relevant MeSH terms:
Heart Defects, Congenital
Heart Diseases
Hypertension
Hypertension, Pulmonary
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Bosentan
Sildenafil
Antihypertensive Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on October 22, 2014