Congenital Heart Disease
Conditions
Keywords
Cardiopulmonary Bypass, ACE inhibitor, Pediatrics
Brief summary
The purpose of this study is to determine whether ACE inhibitors alter the fibrinolytic, inflammatory, and hemodynamic response to cardiopulmonary bypass in infants and children with congenital heart disease.
Interventions
Patients randomized to this group will continue their current dose of ACE inhibitors until surgery
OTHERNo ACE Inhibitor
Patients randomized to this group will stop their ACE inhibitors 48 hours before surgery
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Infants or children (newborn to 17 years of age) undergoing cardiopulmonary bypass for elective surgical correction of a congenital heart defect. * Patients must be taking an ACE inhibitor prior to their operation
Exclusion criteria
* Patients in which discontinuing ACEIs is deemed unsafe by their primary cardiologist * Any condition rendering the subjects legal guardian unable to understand the nature, scope, and possible consequences of the study. * Pregnancy as ruled out by standard of care screening procedures. * Individuals whose weight is less than 3.5 kg at the time of enrollment. * Inability to comply with the protocol. ie. Children in whom it is deemed unsafe to have the extra blood draws, and children who are thought to be noncompliant with their medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | Baseline (prior to surgery), On CPB for 30 minutes, At completion of CPB, and postoperative day 1 (at 8:00AM)postoperative day 1 |
| t-PA (Tissue-type Plasminogen Activator) Antigen | Baseline (prior to surgery) to postoperative day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Bleeding | 24 hours | Chest tube output at 4 and 24 hours after completion of surgery |
| IL-8 (Interleukin-8) | Baseline (pre-surgery) to postoperative day 1 | — |
| IL-6 (Interleukin-6) | Baseline (pre-surgery) to postoperative day 1 | — |
| Postoperative Renal Function | Baseline (prior to surgery) to postoperative day 1 | Acute kidney injury occurring |
| (MAP) Mean Arterial Blood Pressure | Baseline (prior to surgery) to postoperative day 1 | — |
Countries
United States
Participant flow
Pre-assignment details
29 participants were eligible, 8 refused participation
Participants by arm
| Arm | Count |
|---|---|
| ACE Inhibitor Patients already on an ACE inhibitor will continue it until the day of surgery
Angiotensin Converting Enzyme Inhibitor: Patients randomized to this group will continue their current dose of ACE inhibitors until surgery | 11 |
| No ACE Inhibitor Patients on ACE inhibitors who are randomized to stop their ACE inhibitor 48 hours prior to surgery
No ACE Inhibitor: Patients randomized to this group will stop their ACE inhibitors 48 hours before surgery | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | surgery was completed without cardiopulm | 0 | 1 |
Baseline characteristics
| Characteristic | ACE Inhibitor | Total | No ACE Inhibitor |
|---|---|---|---|
| Age, Continuous | 13.7 months STANDARD_DEVIATION 3.5 | 17.2 months STANDARD_DEVIATION 5.02 | 20.8 months STANDARD_DEVIATION 6.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 16 Participants | 7 Participants |
| Region of Enrollment United States | 11 participants | 20 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 13 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 9 |
| other Total, other adverse events | 4 / 11 | 0 / 9 |
| serious Total, serious adverse events | 4 / 11 | 2 / 9 |
Outcome results
Primary
(PAI-1) Plasminogen Activator Inhibitor -1 Antigen
Time frame: Baseline (prior to surgery), On CPB for 30 minutes, At completion of CPB, and postoperative day 1 (at 8:00AM)postoperative day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | Baseline, Pre- Cardiopulmonary bypass (CPD) | 4.59 ng/ml | Standard Error 2.36 |
| ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | at 30 minutes on CPB | 13.59 ng/ml | Standard Error 2.8 |
| ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | Completion of CPB | 54.74 ng/ml | Standard Error 6.63 |
| ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | postoperative day 1 (at 8:00AM) | 57.13 ng/ml | Standard Error 12.14 |
| No ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | postoperative day 1 (at 8:00AM) | 88.74 ng/ml | Standard Error 14.02 |
| No ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | Baseline, Pre- Cardiopulmonary bypass (CPD) | 3.78 ng/ml | Standard Error 0.58 |
| No ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | Completion of CPB | 58.56 ng/ml | Standard Error 0.86 |
| No ACE Inhibitor | (PAI-1) Plasminogen Activator Inhibitor -1 Antigen | at 30 minutes on CPB | 17.8 ng/ml | Standard Error 2.49 |
p-value: 0.03ANOVA
Primary
t-PA (Tissue-type Plasminogen Activator) Antigen
Time frame: Baseline (prior to surgery) to postoperative day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | Baseline, Pre- Cardiopulmonary bypass (CPD) | 10.81 ng/ml | Standard Error 1 |
| ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | On CPB for 30 minutes | 12.97 ng/ml | Standard Error 5.43 |
| ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | At completion of CPB | 16.83 ng/ml | Standard Error 1.84 |
| ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | postoperative day 1 (at 8:00AM) | 14.36 ng/ml | Standard Error 3.05 |
| No ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | postoperative day 1 (at 8:00AM) | 20.24 ng/ml | Standard Error 1.82 |
| No ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | Baseline, Pre- Cardiopulmonary bypass (CPD) | 8.31 ng/ml | Standard Error 0.94 |
| No ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | At completion of CPB | 28.03 ng/ml | Standard Error 3.15 |
| No ACE Inhibitor | t-PA (Tissue-type Plasminogen Activator) Antigen | On CPB for 30 minutes | 20.44 ng/ml | Standard Error 6.38 |
p-value: 0.13ANOVA
Secondary
IL-6 (Interleukin-6)
Time frame: Baseline (pre-surgery) to postoperative day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACE Inhibitor | IL-6 (Interleukin-6) | on CPB for 30min | 9.64 pg/ml | Standard Error 3.23 |
| ACE Inhibitor | IL-6 (Interleukin-6) | postoperative day 1 (at 8:00AM) | 401.69 pg/ml | Standard Error 123.66 |
| ACE Inhibitor | IL-6 (Interleukin-6) | At completion of CPB | 215.84 pg/ml | Standard Error 32.59 |
| ACE Inhibitor | IL-6 (Interleukin-6) | Baseline, Pre- Cardiopulmonary bypass (CPD) | 2.29 pg/ml | Standard Error 1.27 |
| No ACE Inhibitor | IL-6 (Interleukin-6) | At completion of CPB | 141.00 pg/ml | Standard Error 91.56 |
| No ACE Inhibitor | IL-6 (Interleukin-6) | on CPB for 30min | 13.08 pg/ml | Standard Error 3.49 |
| No ACE Inhibitor | IL-6 (Interleukin-6) | Baseline, Pre- Cardiopulmonary bypass (CPD) | 3.06 pg/ml | Standard Error 1.76 |
| No ACE Inhibitor | IL-6 (Interleukin-6) | postoperative day 1 (at 8:00AM) | 119.13 pg/ml | Standard Error 33.54 |
p-value: 0.02ANOVA
Secondary
IL-8 (Interleukin-8)
Time frame: Baseline (pre-surgery) to postoperative day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACE Inhibitor | IL-8 (Interleukin-8) | at 30 minutes on CPB | 20.76 pg/mL | Standard Error 4.57 |
| ACE Inhibitor | IL-8 (Interleukin-8) | postoperative day 1 (at 8:00AM) | 201.05 pg/mL | Standard Error 66.91 |
| ACE Inhibitor | IL-8 (Interleukin-8) | Baseline (Before going on cardiopulmonary bypass | 11.69 pg/mL | Standard Error 2.07 |
| ACE Inhibitor | IL-8 (Interleukin-8) | Admission to ICU following surgery | 213.74 pg/mL | Standard Error 39.39 |
| No ACE Inhibitor | IL-8 (Interleukin-8) | postoperative day 1 (at 8:00AM) | 127.03 pg/mL | Standard Error 42.48 |
| No ACE Inhibitor | IL-8 (Interleukin-8) | at 30 minutes on CPB | 36.91 pg/mL | Standard Error 16.92 |
| No ACE Inhibitor | IL-8 (Interleukin-8) | Admission to ICU following surgery | 244.86 pg/mL | Standard Error 121.13 |
| No ACE Inhibitor | IL-8 (Interleukin-8) | Baseline (Before going on cardiopulmonary bypass | 15.56 pg/mL | Standard Error 3.61 |
p-value: 0.67ANOVA
Secondary
(MAP) Mean Arterial Blood Pressure
Time frame: Baseline (prior to surgery) to postoperative day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | Baseline, Pre- Cardiopulmonary bypass (CPD) | 42.65 mmHg | Standard Error 1.68 |
| ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | at 30 minutes on CPB | 53.02 mmHg | Standard Error 3.16 |
| ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | At completion of CPB | 60.35 mmHg | Standard Error 4.23 |
| ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | postoperative day 1 (at 8:00AM) | 60.63 mmHg | Standard Error 4.23 |
| No ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | postoperative day 1 (at 8:00AM) | 64.16 mmHg | Standard Error 3.33 |
| No ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | Baseline, Pre- Cardiopulmonary bypass (CPD) | 47.82 mmHg | Standard Error 3.6 |
| No ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | At completion of CPB | 59.48 mmHg | Standard Error 3.81 |
| No ACE Inhibitor | (MAP) Mean Arterial Blood Pressure | at 30 minutes on CPB | 53.52 mmHg | Standard Error 2.93 |
Secondary
Postoperative Bleeding
Chest tube output at 4 and 24 hours after completion of surgery
Time frame: 24 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACE Inhibitor | Postoperative Bleeding | Chest tube output in 4 hrs | 38.4 mL/kg | Standard Error 13.8 |
| ACE Inhibitor | Postoperative Bleeding | Chest tube output in 24 hrs | 76.3 mL/kg | Standard Error 20.7 |
| No ACE Inhibitor | Postoperative Bleeding | Chest tube output in 4 hrs | 19.8 mL/kg | Standard Error 2.9 |
| No ACE Inhibitor | Postoperative Bleeding | Chest tube output in 24 hrs | 43.2 mL/kg | Standard Error 6.2 |
Comparison: P-value is for comparison of chest tube output at 24 hoursp-value: 0.47t-test, 2 sided
Secondary
Postoperative Renal Function
Acute kidney injury occurring
Time frame: Baseline (prior to surgery) to postoperative day 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ACE Inhibitor | Postoperative Renal Function | 54.5 Percentage of subject with AKI |
| No ACE Inhibitor | Postoperative Renal Function | 33.3 Percentage of subject with AKI |
p-value: 0.41Fisher Exact