A Comparison of Dilute Versus Concentrated Heparin for CRRT Anticoagulation

NCT01318811 | Terminated Phase 4 Results

• 1 other identifier: VU 110162
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Kidney Injury; Acute Renal Failure; Heart Failure

Keywords

Heparin; CRRT; Continuous renal replacement therapy; CVVHD; Anticoagulation

Outcome Measures

Primary Outcomes (1)

• Filter Life

  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.

  72 hours

Secondary Outcomes (1)

• Number of Major Bleeding Complications

  72 hours

Study Arms (2)

Dilute heparin

ACTIVE COMPARATOR

Arm A will receive dilute heparin delivered as an intravenous infusion proximal to the dialysis filter.

Drug: Dilute unfractionated heparin

Standard concentrated heparin

ACTIVE COMPARATOR

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

Interventions

Dilute unfractionated heparin DRUG

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.

Also known as: Heparin

Dilute heparin

Standard concentration unfractionated heparin DRUG

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.

Also known as: Heparin

Standard concentrated heparin

Eligibility Criteria

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

You may qualify if:

• Age greater than 18 years
• Renal failure, electrolyte disturbance, or volume overload requiring continuous venovenous hemodialysis (CVVHD) as determined by the Nephrology consult service

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• Tolwani AJ, Wille KM. Anticoagulation for continuous renal replacement therapy. Semin Dial. 2009 Mar-Apr;22(2):141-5. doi: 10.1111/j.1525-139X.2008.00545.x.

  PMID: 19426417 BACKGROUND

• 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. doi: 10.1681/ASN.V71145.

  PMID: 8808122 BACKGROUND

• Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3.

  PMID: 33314078 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury; Heart Failure

Interventions

Heparin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Dr. Thomas Golper
• Organization: Vanderbilt_Univeristy MC

thomas.golper@vumc.org

615-322-5914

Study Officials

• Thomas A Golper, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 18, 2011
• Study Start: March 1, 2011
• Primary Completion: April 3, 2016
• Study Completion: April 3, 2016
• Last Updated: February 22, 2019
• Results First Posted: January 29, 2019

Record last verified: 2019-02

Locations

US (1)