Congenital Heart DiseaseNCT01548950
Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension
A study testing Sildenafil singly or in association with Bosentan in people with Congenital Heart Disease and Pulmonary Arterial Hypertension, run by University of Sao Paulo General Hospital at 1 site in Brazil.
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%. Read more about this study
- Who is it for?
- Ages 2 months and older
- Conditions the study is for
- Congenital Heart Disease, Pulmonary Arterial Hypertension
- What is being tested?
- Sildenafil singly or in association with Bosentan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- Sep 2011to Mar 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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%.
Who cannot join
- Patients with complex cardiac anomalies for whom there are no possibilities of complete repair. Patients with uni-ventricular physiology.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combined Clinical and Surgical Approaches to Congenital Heart Disease Associated With Pulmonary Arterial Hypertension (PAH-CHD)
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%.
Read the 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.
- Being tested
- Sildenafil singly or in association with Bosentan
- Keywords
- Congenital heart disease, Pulmonary arterial hypertension, Sildenafil, Bosentan, Pediatric cardiac surgery
- Medical subject headings
- Heart Defects, Congenital, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil singly or in association with BosentanDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single-arm study | Other | 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. Receives: Drug: Sildenafil singly or in association with Bosentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Six months following surgery
Secondary outcomes (1)
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.
Measured: Six months following surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study startSep 2011
- Primary completionJan 2014
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto do Coracao, Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Sponsor
- Investigators
- Antonio Augusto Lopes, M.D., Principal investigator, Instituto do Coração (InCor) - HCFMUSP - São Paulo - Brazil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01548950
- Sponsor's protocol ID
- CAPPesq 0502/11
- Status last verified
- Jun 2015
- First submitted
- 5 Mar 2012
- Last updated
- 30 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Clinical and Surgical Approaches to Congenital Heart Disease Associated With Pulmonary Arterial Hypertension (PAH-CHD)
- ClinicalTrials.gov ID
- NCT01548950
- Acronym / sponsor ID
- CAPPesq 0502/11
- Keywords
- Congenital heart disease, Pulmonary arterial hypertension, Sildenafil, Bosentan, Pediatric cardiac surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- Instituto do Coracao, Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- Sep 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 8 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single-arm study | Other | Drug: Sildenafil singly or in association with BosentanPreoperatively, 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. |
Who may qualify
- Ages
- 2 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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%.
Key exclusion criteria (1 listed)
- Patients with complex cardiac anomalies for whom there are no possibilities of complete repair. Patients with uni-ventricular physiology.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sildenafil singly or in association with BosentanSildenafil, 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. | Drug | Single-arm study |
Primary outcome
Immediate postoperative right cardiac failure and mortality, and prevalence of residual PAH six months after surgery.
Time frame: Six months following 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).
1 secondary outcome
Pulmonary vascular resistance six months after surgical repair of congenital cardiac shunts with PAH
Time frame: Six months following surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Augusto Lopes, M.D. principal investigator
Instituto do Coração (InCor) - HCFMUSP - São Paulo - Brazil
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sildenafil singly or in association with Bosentan in people with Congenital Heart Disease and Pulmonary Arterial Hypertension, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immediate postoperative right cardiac failure and mortality, and prevalence of residual PAH six months after surgery. (time frame: Six months following surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.