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Postoperative HemorrhagePhase 3NCT00307138

Hetastarch and Bleeding Complications After Off-Pump Coronary Bypass Surgery

A Phase 3 study testing hetastarch in people with Postoperative Hemorrhage, run by Kaiser Permanente at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 20 to 80 years
Conditions the study is for
Postoperative Hemorrhage
What is being tested?
hetastarch
How many people
330 participants
Where
1 siteUnited States
Study dates
Sep 2004to Aug 2005
Phase
Phase 3
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 20 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Summit Medical Center

    Oakland, California, 94611

Other trials in United States

About this study

Official title: 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.

Read more

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.

Read the detailed description

Recruitment

  1. Eligibility screening:
  2. All adult Kaiser Permanente members admitted to Summit Hospital (Oakland, CA) for coronary bypass graft surgery which is planned to be conducted off-pump.
  3. Recruitment period: 9/1/2004 through 7/27/05
  4. At recruitment, each subject who agrees to participate is assigned a study number
  5. The study number is assigned sequentially and is totally independent of the medical record number or other personal identifying information
  6. The linkage between the study number and all personal identifying information is kept in a locked file separate from other project data
  7. Exclusion criteria:
  8. pregnancy
  9. patients scheduled to undergo on-pump procedures
  10. patients with a history of any of:
  11. cardiac surgery
  12. primary bleeding disorders
  13. end-stage renal disease.
  14. Statistical power analysis
  15. This study is designed as an equivalence trial
  16. 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.
  17. Statistical power is calculated using the confidence-interval-based technique for normally distributed interval variables.
  18. The confidence interval is set at 95%
  19. The range of equivalence is defined as +100 milliliters
  20. Power is set at 90%
  21. The target sample size which results from this analysis is 165 patients in each arm (i.e., hetastarch and albumin).
  22. Analytic strategy
  23. All project analyses are conducted by intention-to-treat
  24. 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.
  25. Confidence intervals are calculated using the exact techniques
  26. 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.
  27. Intervention process
  28. When the patient is in the operating room, the anesthesiologist opens the envelope containing the study group assignment (i.e., hetastarch or albumin).
  29. The attending anesthesiologist administers 1 liter of 6% hetastarch intraoperatively to patients from the study group.
  30. The attending anesthesiologist administers 1 liter of albumin intraoperatively to patients from the study group.
  31. 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.
  32. All patients receive the remaining standard operative regimen of crystalloids and blood products at the discretion of the anesthesiologist.
  33. All patients are transferred postoperatively to the Intensive Care Unit.
  34. The attending intensivists are blinded to the patient's randomization assignment
  35. The attending intensivists use standard fluid replacement at their clinical discretion.
  36. No hetastarch is administered in the intensive care unit.
  37. Measurements
  38. Preoperative
  39. age
  40. gender
  41. body mass index
  42. type of surgery
  43. (elective vs. urgent/emergent)
  44. serum albumin level
  45. serum creatinine level
  46. blood urea nitrogen level
  47. hematocrit
  48. platelet count
  49. prothrombin time
  50. partial thromboplastin time
  51. preoperative administration of anticoagulants
  52. preoperative administration of antiplatelet medications
  53. preoperative administration of thrombolytic agents
  54. Perioperative
  55. identity of the surgeon
  56. identity of the anesthesiologist
  57. lowest body temperature
  58. highest activated clotting time
  59. volume of crystalloids
  60. volume of colloids
  61. volume of cell-saver
  62. number of units of blood products administered
  63. Postoperative
  64. hourly chest tube drainage in the first 12 postoperative hours
  65. volume of crystalloid delivered
  66. volume of albumin delivered
  67. number of units of blood products transfused
  68. whether reoperation for postoperative bleeding was required
  69. duration of mechanical ventilation
  70. duration of stay in the intensive care unit
  71. total length of hospital stay
  72. mortality rates for patients treated in the ICU
  73. mortality rates for patients treated in other inpatient areas of the hospital.
Being tested
hetastarch
Keywords
Coronary artery bypass, Off-pump, Hetastarch, Plasma substitutes, Equivalence
Medical subject headings
Postoperative Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • hetastarchDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. the number of units of packed red blood cells transfused within the first 24 hours after surgery

  2. the number of units of fresh-frozen plasma transfused within the first 24 hours after surgery

  3. the number of units of platelets transfused within the first 24 hours after surgery

Secondary outcomes (6)

  1. volume of chest tube drainage within the first 12 postoperative hours

  2. reoperation for bleeding complications

  3. duration of mechanical ventilation

  4. length of stay in the intensive care unit

  5. length of total postoperative hospital stay

  6. ; and total mortality rates

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2006 (estimated)
  2. Study startSep 2004
  3. Study completionAug 2005

Resources

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Enrolment
330 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00307138
Sponsor's protocol ID
Hetastarch_Off-pump_CABG
Status last verified
Aug 2005
First submitted
24 Mar 2006
Last updated
22 May 2006
Results posted
No

Publications

  • Avorn J, Patel M, Levin R, Winkelmayer WC. Hetastarch and bleeding complications after coronary artery surgery. Chest. 2003 Oct;124(4):1437-42. doi: 10.1378/chest.124.4.1437.

    PubMed 14555577

  • Kirklin JK, Lell WA, Kouchoukos NT. Hydroxyethyl starch versus albumin for colloid infusion following cardiopulmonary bypass in patients undergoing myocardial revascularization. Ann Thorac Surg. 1984 Jan;37(1):40-6. doi: 10.1016/s0003-4975(10)60707-2.

    PubMed 6197944

  • Tigchelaar I, Gallandat Huet RC, Korsten J, Boonstra PW, van Oeveren W. Hemostatic effects of three colloid plasma substitutes for priming solution in cardiopulmonary bypass. Eur J Cardiothorac Surg. 1997 Apr;11(4):626-32. doi: 10.1016/s1010-7940(96)01059-7.

    PubMed 9151028

  • Brutocao D, Bratton SL, Thomas JR, Schrader PF, Coles PG, Lynn AM. Comparison of hetastarch with albumin for postoperative volume expansion in children after cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1996 Apr;10(3):348-51. doi: 10.1016/s1053-0770(96)80095-4.

    PubMed 8725415

  • London MJ, Ho JS, Triedman JK, Verrier ED, Levin J, Merrick SH, Hanley FL, Browner WS, Mangano DT. A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations. J Thorac Cardiovasc Surg. 1989 May;97(5):785-97.

    PubMed 2468978

  • Sade RM, Stroud MR, Crawford FA Jr, Kratz JM, Dearing JP, Bartles DM. A prospective randomized study of hydroxyethyl starch, albumin, and lactated Ringer's solution as priming fluid for cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1985 May;89(5):713-22.

    PubMed 2581099

  • Jones B, Jarvis P, Lewis JA, Ebbutt AF. Trials to assess equivalence: the importance of rigorous methods. BMJ. 1996 Jul 6;313(7048):36-9. doi: 10.1136/bmj.313.7048.36.

    PubMed 8664772

  • Hecht-Dolnik M, Barkan H, Taharka A, Loftus J. Hetastarch increases the risk of bleeding complications in patients after off-pump coronary bypass surgery: a randomized clinical trial. J Thorac Cardiovasc Surg. 2009 Sep;138(3):703-11. doi: 10.1016/j.jtcvs.2009.02.035. Epub 2009 May 27.

    PubMed 19698859

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing hetastarch in people with Postoperative Hemorrhage, run by Kaiser Permanente at 1 site in United States.

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 4 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 22 May 2006. 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 United States. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

the number of units of packed red blood cells transfused within the first 24 hours after surgery. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00307138, which also lists 8 linked publications.

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 22 May 2006.

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