Hetastarch and Bleeding Complications After Off-Pump Coronary Bypass Surgery

May 19, 2006 updated by: Kaiser Permanente

Hetastarch (Hextend) and Bleeding Complications After Off-Pump Coronary Bypass Surgery

There has been continuing debate about whether use of hetastarch for volume replacement in coronary artery bypass surgery [CABG] increases the risk of postoperative bleeding. A recent meta-analysis of hetastarch use in on-pump CABG concluded that use of hetastarch in these procedures is associated with increased risk, but the safety of hetastarch use in off-pump procedures remains unresolved.

We designed a double-blinded randomized clinical trial to investigate this question. The study was designed as an equivalence trial. Statistical power calculations were performed taking this into consideration. Sealed assignments from a block randomization table developed prior nto initiation of the trial were unsealed in the operating room. These were used to assign patients scheduled for off-pump CABG to receive either 1 L of hetastarch or 1 L of albumin as part of intraoperative volume replacement. Albumin was used for all subsequent intraoperative and postoperative fluid replacement.

The rate of postoperative bleeding was assessed prospectively by monitoring hourly chest tube drainage and number of units of blood products transfused postoperatively in the Intensive Care Unit. Risk was assessed by a Data Safety Monitoring Committee (DSMC) established for this trial. The SAMC was scheduled per protocol to meet after the first 15 subjects (both groups combined) had 1000cc or more of chest tube drainage in the first 12 hours postoperative, and then subsequently either after 15 additional bleeds of this volume or following a schedule set at the discretion of the DSMC.

The trial was continued until 156 patients had been recruited. At that time, 78 participants each had been assigned to the hetastarch and albumin groups. DSMC review at that time determined that use of hetastarch is associated with a risk of postoperative bleeding which is greater than the risk associated with use of albumin and the DSMC accordingly halted the trial.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Recruitment

  1. Eligibility screening:

    a. All adult Kaiser Permanente members admitted to Summit Hospital (Oakland, CA) for coronary bypass graft surgery which is planned to be conducted off-pump.

  2. Recruitment period: 9/1/2004 through 7/27/05

    1. At recruitment, each subject who agrees to participate is assigned a study number

      1. The study number is assigned sequentially and is totally independent of the medical record number or other personal identifying information
      2. The linkage between the study number and all personal identifying information is kept in a locked file separate from other project data

  3. Exclusion criteria:

    1. pregnancy
    2. patients scheduled to undergo on-pump procedures

    3. patients with a history of any of:

      1. cardiac surgery
      2. primary bleeding disorders
      3. end-stage renal disease.

  4. Statistical power analysis

    1. This study is designed as an equivalence trial
    2. Target outcome rates are based on those published in Sade RM, Stroud MR, Crawford FA Jr, et al. J Thorac Cardiovasc Surg 1985 May;89(5):713-22.

    3. Statistical power is calculated using the confidence-interval-based technique for normally distributed interval variables.

      1. The confidence interval is set at 95%
      2. The range of equivalence is defined as +100 milliliters
      3. Power is set at 90%
    4. The target sample size which results from this analysis is 165 patients in each arm (i.e., hetastarch and albumin).

  5. Analytic strategy

    1. All project analyses are conducted by intention-to-treat

    2. Bivariate comparisons between the study (i.e., hetastarch) and control (i.e., albumin) group measurements use the Fisher exact test or Student's t test for independent samples as appropriate given the nature of the measurement were used to conduct bivariate comparisons of study group measures with control group measures.

      1) Confidence intervals are calculated using the exact techniques

    3. Multivariate comparisons: Analysis of variance and general linear modeling are used to conduct multivariate comparisons of measures between the study and control groups while controlling for covariates.

  6. Intervention process

    1. When the patient is in the operating room, the anesthesiologist opens the envelope containing the study group assignment (i.e., hetastarch or albumin).

      1. The attending anesthesiologist administers 1 liter of 6% hetastarch intraoperatively to patients from the study group.
      2. The attending anesthesiologist administers 1 liter of albumin intraoperatively to patients from the study group.
    2. After the first liter of colloid is administered, the patients receive only albumin if more colloid is needed to meet additional requirements for fluid replacement.
    3. All patients receive the remaining standard operative regimen of crystalloids and blood products at the discretion of the anesthesiologist.

    4. All patients are transferred postoperatively to the Intensive Care Unit.

      1. The attending intensivists are blinded to the patient's randomization assignment
      2. The attending intensivists use standard fluid replacement at their clinical discretion.
      3. No hetastarch is administered in the intensive care unit.

  7. Measurements

    1. Preoperative

      1. age
      2. gender
      3. body mass index

      4. type of surgery

        a) (elective vs. urgent/emergent)

      5. serum albumin level
      6. serum creatinine level
      7. blood urea nitrogen level
      8. hematocrit
      9. platelet count
      10. prothrombin time
      11. partial thromboplastin time
      12. preoperative administration of anticoagulants
      13. preoperative administration of antiplatelet medications
      14. preoperative administration of thrombolytic agents

    2. Perioperative

      1. identity of the surgeon
      2. identity of the anesthesiologist
      3. lowest body temperature
      4. highest activated clotting time
      5. volume of crystalloids
      6. volume of colloids
      7. volume of cell-saver
      8. number of units of blood products administered

    3. Postoperative

      1. hourly chest tube drainage in the first 12 postoperative hours
      2. volume of crystalloid delivered
      3. volume of albumin delivered
      4. number of units of blood products transfused
      5. whether reoperation for postoperative bleeding was required
      6. duration of mechanical ventilation
      7. duration of stay in the intensive care unit
      8. total length of hospital stay
      9. mortality rates for patients treated in the ICU
      10. mortality rates for patients treated in other inpatient areas of the hospital.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
330

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

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
    • California
      • Oakland, California, United States, 94611
        • Summit Medical Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Scheduled coronary bypass graft surgery that is planned to be conducted on adults off-pump (i.e., without use of cardio-pulmonary bypass).

Exclusion Criteria:

  • Scheduled coronary bypass graft surgery that is planned to be conducted on adults on-pump (i.e., with use of cardio-pulmonary bypass).
  • A history of cardiac surgery
  • A history of primary bleeding disorders
  • End-stage renal disease

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: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
the number of units of packed red blood cells transfused within the first 24 hours after surgery
the number of units of fresh-frozen plasma transfused within the first 24 hours after surgery
the number of units of platelets transfused within the first 24 hours after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
duration of mechanical ventilation
volume of chest tube drainage within the first 12 postoperative hours
reoperation for bleeding complications
length of stay in the intensive care unit
length of total postoperative hospital stay
; and total mortality rates

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kaiser Permanente

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Kaiser Foundation Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marketa Hecht, MD, Kaiser Permanente

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2004

Study Completion

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2005

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2006

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 22, 2006

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2006

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Hetastarch_Off-pump_CABG

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