Hetastarch and Bleeding Complications After Off-Pump Coronary Bypass Surgery

NCT00307138 | Completed Phase 3

• 1 other identifier: Hetastarch_Off-pump_CABG
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

Brief 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, 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.

Conditions

Postoperative Hemorrhage

Keywords

Coronary artery bypass, Off-pump; Hetastarch; Plasma substitutes; Equivalence

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• volume of chest tube drainage within the first 12 postoperative hours

• reoperation for bleeding complications

• duration of mechanical ventilation

• length of stay in the intensive care unit

• length of total postoperative hospital stay

Interventions

hetastarch DRUG

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kaiser Permanente: lead
• Kaiser Foundation Research Institute: collaborator

Study Sites (1)

Summit Medical Center

Oakland, California, 94611, United States

Location

Related Publications (8)

• 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.

  PMID: 14555577 BACKGROUND

• 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.

  PMID: 6197944 BACKGROUND

• 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.

  PMID: 9151028 BACKGROUND

• 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.

  PMID: 8725415 BACKGROUND

• 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.

  PMID: 2468978 BACKGROUND

• 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.

  PMID: 2581099 BACKGROUND

• 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.

  PMID: 8664772 BACKGROUND

• 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.

  PMID: 19698859 DERIVED

MeSH Terms

Conditions

Postoperative Hemorrhage

Interventions

Hydroxyethyl Starch Derivatives

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications

Intervention Hierarchy (Ancestors)

Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Study Officials

• Marketa Hecht, MD

  Kaiser Permanente

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 24, 2006
• First Posted: March 27, 2006
• Study Start: September 1, 2004
• Study Completion: August 1, 2005
• Last Updated: May 22, 2006

Record last verified: 2005-08

Locations

US (1)