Clinical trial NCT03576534: Pre Bypass Ultrafiltration (PBUF) in Children Requiring Cardiopulmonary Bypass
Official title: Pre Bypass Ultrafiltration (PBUF) Improves Intraoperative Glucose, Sodium, Potassium and Lactate Levels in Children Requiring Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Congenital Heart Disease
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2018-07-03
Enrollment: 13
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Control Trial
Primary purpose: TREATMENT

Brief summary: Newborn babies and children with congenital heart defects who need heart surgery need to be placed on the heart-lung machine for heart surgery.

In order to use the heart-lung machine, the investigators have to use blood and other fluids to fill the tubing. During the operation, ultrafiltration is carried out as standard of care to remove extra fluid. Modified ultrafiltration is also performed after surgery. In this study, the investigators are looking to use the filter additionally before surgery. Using the pre bypass filtration before the subject is placed on the heart-lung machine will allow the investigators to better normalize electrolytes in the blood/fluid mixture used in the heart lung machine. This technique is called pre-bypass ultrafiltration, or PBUF (pronounced "P" Buff).

The investigators are conducting a study to see if using PBUF to better normalize electrolytes in the blood will make a difference. The investigators have been adding fluids to prime the heart-lung machine in two different ways. The investigators believe both methods are safe and acceptable but hypothesize that there may be subtle differences in electrolytes and fluid status when one technique is used as opposed to the other. The investigators believe that neither technique introduces risk since both are currently used in practice. The standard method adds blood to the heart-lung machine. The alternate method adds blood to the heart-lung machine and then additional fluid is added and removed to more normalize the electrolytes. The investigators plan to randomized subjects undergoing heart surgery to receive the standard priming method versus PBUF to determine if there is any difference in outcomes. Laboratory and clinical data collected as part of clinical care will be used to determine difference sin outcomes. There will be no additional blood taken for this study.

There are no known risks to PBUF. The benefits include helping investigators determine if PBUF does or does not make a difference to how subjects recover after surgery. The investigators believe that providing more normal blood values will either improve the subjects' outcome or have no benefit. The investigators do not anticipate increased risks.

Given COVID -19 restrictions, the study is on hold.

Detailed description: Research question: Can PBUF provide more physiologic values for glucose, sodium, potassium and lactate throughout the cardiopulmonary bypass period without an increased incidence of adverse events?

Background: The values for glucose, sodium, potassium and lactate in blood primes for subjects weighing less than 8 kg are known to be non-physiologic. The process of priming the cardiopulmonary bypass circuit is not standardized across institutions and there are several methods used to correct for known prime value issues. The investigators documented the prime values for 20 subjects weighing less than 8 kg and then performed pre-bypass ultrafiltration (PBUF) on the prime for those same circuits to achieve more physiologic prime values. The investigators were cautious not to implement too significant of a change as the investigators assessed the technique and documented that plasma-free hemoglobin importantly did not rise and that measured osmolality was still slightly above the normal range.

Study type: Prospective randomized controlled study.

Hypothesis: The investigators hypothesize that pre cardiopulmonary bypass ultrafiltration (PBUF) can provide more physiologic prime values for glucose, sodium, potassium and lactate. Plasma-free hemoglobin will not increase with the technique. Osmolality will be maintained slightly above the normal range. PBUF will not negatively impact clinical outcome measures and may improve them.

Specific Aim 1 To determine if use of PBUF will result in more physiologic values for glucose, sodium, potassium and lactate during and immediately after cardiopulmonary bypass.

Specific Aim 2 To determine if PBUF can be achieved with no increase in plasma free hemoglobin while maintaining plasma osmolality within acceptable range during and immediately after cardiopulmonary bypass.

Specific Aim 3 To determine if use of PBUF will result in improved clinical outcomes after surgery on cardiopulmonary bypass.

Randomization: Prior to surgery, subjects will be randomized to one of the two study groups using a randomly permuted blocks design.

Statistical analysis: Analyses will be performed on an intention to treat basis. Comparisons of subject characteristics and outcomes will be made using the two-sample t test or Wilcoxon rank sum test for continuous variables, and Fisher's exact test for categorical variables. If imbalances in patient factors exist between the two groups, linear and logistic regression will be used to compare outcomes for the groups adjusting for these potential confounders.

Sample size calculation: Sample size is calculated for comparisons of subjects in the normal range of values for the PBUF and standard care groups. This will be done separately for glucose, sodium, potassium, and lactate; each comparison will be performed at the 0.0125 level of significance. If 70% of standard care subjects are in the normal range versus 90% of PBUF subjects, a total of 176 subjects (88 per group) would be required to achieve 80% power. With 350 eligible subjects that meet inclusion criteria based on 2017 numbers and 75% consent rate the investigators will be able to enroll 260 subjects in 1 year.

Given COVID-19 restrictions, the study is on hold.

Eligibility criteria: Inclusion Criteria:

* All patients \< 8 kilograms and \< 1 year (to ensure that all patients receive steroids at initiation of CPB) undergoing an index cardiac operation for that hospitalization (using a single PBUF protocol)

Exclusion Criteria:

* Patients undergoing repeat cardiac surgery within the same admission
* Patients undergoing transplants as their index surgery
* Patients undergoing Ventricular assist device implantation as their index surgery

Primary outcomes:
measure: Glucose in milligrams per deciliter (mg/dL). Normal range 61 to 199 mg/dL
timeFrame: 12 hours
measure: Sodium in milliequivalents per liter (mEq/L). Normal range 135 to 148 mEq/L
timeFrame: 12 hours
measure: Potassium in milliequivalents per liter (mEq/L). Normal range 3.2 to 4.5 mEg/L
timeFrame: 12 hours
measure: Lactate in milliequivalents per liter (mEq/L). Normal range 0.5 to 2.2 mEq/L
timeFrame: 12 hours
Secondary outcomes:
measure: Osmolality in milli osmoles per kilogram (mOsm/Kg). Normal Range 276- 295 mOsm/kg
timeFrame: 12 hours
measure: Plasma free hemoglobin in milligrams per deciliter (mg/dL). Normal < 5 mg/dL.
timeFrame: 12 hours
measure: Inotrope use
timeFrame: 72 hours
measure: Body wall edema as measured daily weights in kilograms (Kg)
timeFrame: Through study completion (until hospital discharge), an average of 15 days.
measure: Body wall edema as measured daily weights in kilograms (Kg)
timeFrame: Through study completion (until hospital discharge) , an average of 15 days.
measure: Initial ventilation duration in days and hours
timeFrame: Through study completion (until hospital discharge), an average of 15 days.
measure: Reintubation as a proportion subjects needing reintubation in each group Reintubation
timeFrame: Through study completion (until hospital discharge), an average of 15 days.
measure: Total ventilation duration (days, hours)
timeFrame: Through study completion (until hospital discharge), an average of 15 days.
measure: Postoperative Cardiac intensive care unit (CICU) length of stay (LOS) in days,
timeFrame: Through study completion (until hospital discharge), an average of 15 days.
measure: Postoperative hospital LOS
timeFrame: Through study completion (until hospital discharge), an average of 15 days.
measure: Composite of major adverse events (Postoperative extra corporeal membrane oxygenation (ECMO), reoperation for bleeding, reoperation for low cardiac output state, circuit clotting events) and mortality. Yes or No
timeFrame: Through study completion (until hospital discharge), an average of 15 days.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Meena Nathan, MD, MPH
role: STUDY_CHAIR
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