A Comparison of Dilute Versus Concentrated Heparin for CRRT Anticoagulation

Condition(s) targeted: Acute Kidney Injury; Acute Renal Failure; Heart Failure

Intervention: Dilute unfractionated heparin (Drug); Standard concentration unfractionated heparin (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Vanderbilt University

Official(s) and/or principal investigator(s):
Thomas A Golper, MD, Principal Investigator, Affiliation: Vanderbilt University

Overall contact:
Gayle M Vranic, MD, Phone: (615) 480-4969, Email: gayle.vranic@vanderbilt.edu

Heparin is commonly used for anticoagulation of the extracorporeal circuit during continuous renal replacement therapy (CRRT) but the optimal mode of delivery has not yet been validated. Our study will compare dilute heparin to a standard concentration of heparin. The investigators hypothesize that heparin delivered in a dilute solution will augment coating of the filter fibers with anticoagulants, decreasing clotting events and increasing filter life. By improving delivery of heparin to the filter and circuit, where clotting events can disrupt dialysis, less heparin would be required for the extra-corporeal circuit and thus less heparin would be delivered back to the patient with blood return from the machine. By exposing the patient to less heparin it is hypothesized that fewer bleeding events would occur, making the dialysis treatment safer. If more of the filter's fibers remain patent and the filter is functional for a longer period of time, the CRRT would also be more effective.

Official title: A Comparison of Dilute Unfractionated Heparin and Standard Concentrated Unfractionated Heparin Protocols for Anticoagulation of the Extra-corporeal Circuit During Continuous Renal Replacement Therapy in the ICU

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Filter life

Secondary outcome: Bleeding complications

Detailed description: Our study will compare two protocols using heparin for anticoagulation of the extra-corporeal circuit during CRRT. Study subjects will be recruited from patients started on continuous venovenous hemodialysis (CVVHD) in all intensive care units at Vanderbilt University Medical Center (VUMC). Once enrolled, patients will be randomized into one of two study arms. Arm A will receive dilute heparin and arm B will receive standard concentrated heparin and as is standard practice, heparin will be delivered as an intravenous infusion proximal to the dialysis filter in both groups. Replacement of the extra-corporeal circuit, including the dialysis filter, is performed under several circumstances: stopping of CRRT when the subject is transported out of the ICU for a procedure or study, machine malfunction, and clotting of the filter. All CRRT circuits and filters, regardless of patency, are replaced at 72 hours per our dialysis unit protocol. Only data from the first filter used for CVVHD will be used and the study subject's enrollment will end with replacement of the extracorporeal circuit and filter.

Study subjects will receive standard care for the duration of the study and the inpatient Nephrology team will control all aspects of the dialysis treatment. Changes to the heparin infusion rates will be made based on the heparin nomogram for this study. A copy of this nomogram will be provided to the inpatient Nephrology team who will make adjustments to the heparin infusion as required to maintain blood anticoagulation levels at goal. The principle investigators (PIs) will be available at all times by pager and phone to address questions regarding proper adjustment of the heparin infusion and will monitor each heparin dosing change to ensure consistency in implementation of the study protocol.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age greater than 18 years

- Renal failure, electrolyte disturbance, or volume overload requiring continuous

venovenous hemodialysis (CVVHD) as determined by the Nephrology consult service

Exclusion Criteria:

- Age less than 18 years

- Active bleeding

- Coagulopathy as defined by baseline INR > 1. 8, aPTT > 45 seconds, or platelet count <

50 thousand/μL

- Active administration of systemic anticoagulation (such as warfarin, therapeutic

unfractionated heparin, or therapeutic enoxaparin)

- Contraindication to heparin (allergy, thrombocytopenia with platelet count < 50,

known or suspected heparin induced thrombocytopenia [HIT])

- Contraindication to systemic anticoagulation (recent surgical or other invasive

procedure, significant bleeding disorder, concern for intracranial bleeding, or other contraindication as determined by treating physician)

- Administration of drotrecogin (Xigris™)

- Anticipated surgical or other invasive procedure that would necessitate withdrawal of

anticoagulation within 72 hours

- Expected termination of continuous renal replacement therapy (CRRT) or death in < 24

hours

- The need for more than 500 cc an hour of IV fluids delivered proximal to the filter

for the purpose of performing continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF)

Gayle M Vranic, MD, Phone: (615) 480-4969, Email: gayle.vranic@vanderbilt.edu

Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States; Recruiting
Gayle M Vranic, MD, Phone: 615-480-4969, Email: gayle.vranic@vanderbilt.edu
Thomas A Golper, MD, Phone: (615) 343-2220, Email: thomas.golper@vanderbilt.edu
Thomas A Golper, MD, Principal Investigator
Gayle M Vranic, MD, Sub-Investigator

Related publications:

Tolwani AJ, Wille KM. Anticoagulation for continuous renal replacement therapy. Semin Dial. 2009 Mar-Apr;22(2):141-5. Review.

van de Wetering J, Westendorp RG, van der Hoeven JG, Stolk B, Feuth JD, Chang PC. Heparin use in continuous renal replacement procedures: the struggle between filter coagulation and patient hemorrhage. J Am Soc Nephrol. 1996 Jan;7(1):145-50.

Starting date: March 2011
Last updated: March 17, 2011