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A Comparison of Dilute Versus Concentrated Heparin for CRRT Anticoagulation

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Thomas Golper, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01318811
First received: March 17, 2011
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Acute Kidney Injury
Acute Renal Failure
Heart Failure
Drug: Dilute unfractionated heparin
Drug: Standard concentration unfractionated heparin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Filter life [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    The primary endpoint for this study will be the difference in filter life in hours between the group receiving dilute heparin and the group receiving standard concentrated heparin.


Secondary Outcome Measures:
  • Bleeding complications [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    Information on minor bleeding complications, major bleeding complications, and need for blood product transfusions will be collected.


Estimated Enrollment: 200
Study Start Date: March 2011
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dilute heparin
Arm A will receive dilute heparin delivered as an intravenous infusion proximal to the dialysis filter.
Drug: Dilute unfractionated heparin
Patients in the dilute heparin arm will receive a systemic loading dose of heparin of 15 units per kilogram of weight by rapid intravenous bolus. Then a maintenance rate of heparin of 7.5 U/Kg per hour will be started. Heparin will be delivered as a solution of 2 units/mL and the infusion will be prepared with 2,000 units of heparin in 1,000 mL of 0.9% NaCl and delivered intravenously proximal to the dialysis filter.
Other Name: Heparin
Active Comparator: Standard concentrated heparin
Arm B will receive standard concentrated heparin and will be delivered as an intravenous infusion proximal to the dialysis filter.
Drug: Standard concentration unfractionated heparin
Patients in the standard heparin arm will receive a systemic loading dose of heparin of 15 units per kilogram of weight by rapid intravenous bolus. Then a maintenance rate of heparin of 7.5 U/Kg per hour will be started and delivered in a standard concentration intravenously proximal to the dialysis filter via a syringe. The concentration of heparin used will be 1,000 units of heparin per 1 mL of 0.9% NaCl.
Other Name: Heparin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01318811

Contacts
Contact: Thomas A Golper, MD (615) 343-2220 thomas.golper@vanderbilt.edu
Contact: Mohammed Sika, PhD (615) 936-2630 mohammed.sika@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Thomas A Golper, MD    615-343-2220    thomas.golper@vanderbilt.edu   
Contact: Mohammed Sika, PhD    (615) 936-2630    mohammed.sika@vanderbilt.edu   
Principal Investigator: Thomas A Golper, MD         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Thomas A Golper, MD Vanderbilt University
  More Information

Publications:
Responsible Party: Thomas Golper, Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01318811     History of Changes
Other Study ID Numbers: VU 110162
Study First Received: March 17, 2011
Last Updated: June 27, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Heparin
CRRT
Continuous renal replacement therapy
CVVHD
Anticoagulation

Additional relevant MeSH terms:
Acute Kidney Injury
Heart Failure
Renal Insufficiency
Cardiovascular Diseases
Heart Diseases
Kidney Diseases
Urologic Diseases
Calcium heparin
Heparin
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014