Pre Bypass Ultrafiltration (PBUF) in Children Requiring Cardiopulmonary Bypass (PBUF)

February 14, 2022 updated by: Meena Nathan, Boston Children's Hospital

Pre Bypass Ultrafiltration (PBUF) Improves Intraoperative Glucose, Sodium, Potassium and Lactate Levels in Children Requiring Cardiopulmonary Bypass

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 1 year (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Control
Standard of care
ACTIVE_COMPARATOR: Study
PBUF used prior to Cardiopulmonary bypass
Other: Use of prebypass ultrafiltration (PBUF)
In addition to standard of care for cardiopulmonary bypass, in the study arm prebypass ultrafiltration will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose in milligrams per deciliter (mg/dL). Normal range 61 to 199 mg/dL
Time Frame: 12 hours

Differences in glucose (mg/dl) at the following time points, and also differences in the percentage of values within the normal range for each time point, for PBUF versus standard care.

  1. Final prime value (in the PBUF group after completion of PBUF and prior to cardio pulmonary bypass (CPB), in the control group prior to CPB)
  2. First measured levels on bypass - typically 10 minutes post initiation of bypass
  3. Last value on CPB
  4. Last value in OR
  5. First arrival to ICU
12 hours
Sodium in milliequivalents per liter (mEq/L). Normal range 135 to 148 mEq/L
Time Frame: 12 hours

Differences in sodium (mEq/L) at the following time points, and also differences in the percentage of values within the normal range for each time point, for PBUF versus standard care.

  1. Final prime value (in the PBUF group after completion of PBUF and prior to cardio pulmonary bypass (CPB), in the control group prior to CPB)
  2. First measured levels on bypass - typically 10 minutes post initiation of bypass
  3. Last value on CPB
  4. Last value in OR
  5. First arrival to ICU
12 hours
Potassium in milliequivalents per liter (mEq/L). Normal range 3.2 to 4.5 mEg/L
Time Frame: 12 hours

Differences in potassium (mEq/L) at the following time points, and also differences in the percentage of values within the normal range for each time point, for PBUF versus standard care.

  1. Final prime value (in the PBUF group after completion of PBUF and prior to cardio pulmonary bypass (CPB), in the control group prior to CPB)
  2. First measured levels on bypass - typically 10 minutes post initiation of bypass
  3. Last value on CPB
  4. Last value in OR
  5. First arrival to ICU
12 hours
Lactate in milliequivalents per liter (mEq/L). Normal range 0.5 to 2.2 mEq/L
Time Frame: 12 hours

Differences in lactate (mEq/L) at the following time points, and also differences in the percentage of values within the normal range for each time point, for PBUF versus standard care.

  1. Final prime value (in the PBUF group after completion of PBUF and prior to cardio pulmonary bypass (CPB), in the control group prior to CPB)
  2. First measured levels on bypass - typically 10 minutes post initiation of bypass
  3. Last value on CPB
  4. Last value in OR
  5. First arrival to ICU
12 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Osmolality in milli osmoles per kilogram (mOsm/Kg). Normal Range 276- 295 mOsm/kg
Time Frame: 12 hours
Differences in osmolality in mOsm/Kg in final prime, first blood draw after CPB and on arrival to cardiac intensive care unit (CICU) for PBUF versus standard care.
12 hours
Plasma free hemoglobin in milligrams per deciliter (mg/dL). Normal < 5 mg/dL.
Time Frame: 12 hours
Differences in plasma free hemoglobin in mg/dL in final prime, first blood draw after CPB and on arrival to cardiac intensive care unit (CICU) for PBUF versus standard care.
12 hours
Inotrope use
Time Frame: 72 hours

Differences in vasoactive inotrope score between the PBUF and standard care groups at the following time points:

i. Between cessation of CPB and admission to CICU as measured by vasoactive inotrope score (VIS) ii. In CICU as measure by VIS/ 24 hours for first 72 hours
72 hours
Body wall edema as measured daily weights in kilograms (Kg)
Time Frame: Through study completion (until hospital discharge), an average of 15 days.
Differences in body wall edema as measure by daily weights in Kg between the PBUF and standard care groups.
Through study completion (until hospital discharge), an average of 15 days.
Body wall edema as measured daily weights in kilograms (Kg)
Time Frame: Through study completion (until hospital discharge) , an average of 15 days.
Differences in body wall edema as measure by daily weights in Kg between the PBUF and standard care groups.
Through study completion (until hospital discharge) , an average of 15 days.
Initial ventilation duration in days and hours
Time Frame: Through study completion (until hospital discharge), an average of 15 days.
Differences in ventilation duration, Initial (days, hours) until first extubation between the PBUF and standard care groups.
Through study completion (until hospital discharge), an average of 15 days.
Reintubation as a proportion subjects needing reintubation in each group Reintubation
Time Frame: Through study completion (until hospital discharge), an average of 15 days.
Difference in proportion of subjects requiring unplanned reintubation for respiratory failure between the PBUF and standard care groups.
Through study completion (until hospital discharge), an average of 15 days.
Total ventilation duration (days, hours)
Time Frame: Through study completion (until hospital discharge), an average of 15 days.
Difference in total ventilation duration (includes all periods on the ventilator including period following unplanned reintubation for respiratory failure between the PBUF and standard care groups.
Through study completion (until hospital discharge), an average of 15 days.
Postoperative Cardiac intensive care unit (CICU) length of stay (LOS) in days,
Time Frame: Through study completion (until hospital discharge), an average of 15 days.
Difference in postoperative CICU LOS in days between the PBUF and standard care groups.
Through study completion (until hospital discharge), an average of 15 days.
Postoperative hospital LOS
Time Frame: Through study completion (until hospital discharge), an average of 15 days.
Difference in postoperative hospital LOS in days between the PBUF and standard care groups.
Through study completion (until hospital discharge), an average of 15 days.
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
Time Frame: Through study completion (until hospital discharge), an average of 15 days.
Difference in proportion subjects who have a composite event between the PBUF and standard care groups.
Through study completion (until hospital discharge), an average of 15 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Investigators

  • Study Chair: Meena Nathan, MD, MPH, Boston Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 3, 2019

Primary Completion (ACTUAL)

September 13, 2021

Study Completion (ACTUAL)

September 13, 2021

Study Registration Dates

First Submitted

May 29, 2018

First Submitted That Met QC Criteria

June 21, 2018

First Posted (ACTUAL)

July 3, 2018

Study Record Updates

Last Update Posted (ACTUAL)

March 2, 2022

Last Update Submitted That Met QC Criteria

February 14, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P00028603

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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