A Phase 4 interventional study of Dilute unfractionated heparin and Standard concentration unfractionated heparin in Acute Kidney Injury, Acute Renal Failure and Heart Failure, sponsored by Vanderbilt University. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-22.
Sponsored by Vanderbilt University · Phase 4, Interventional, and Treatment
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.
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 pragmatic cluster-randomized (by month of entry) into one of two study arms. Arm A will receive dilute heparin and arm B will receive standard concentrated heparin as both approaches are standard practices at VUMC. 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 and it applies to either arm. 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.
The following is a summary for the two interventions (arms):
Treatment Algorithm Dilute heparin: Patients in the dilute heparin arm (enrolled in odd calendar months) will receive a systemic loading dose of heparin of 15 units per kilogram of weight (all heparin doses will be rounded to the nearest 100 units) by rapid (\< 10 seconds) intravenous bolus. The heparin concentration for the rapid intravenous loading bolus is 1000 units per mL. 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.
Standard concentrated heparin: Patients in the concentrated heparin arm (enrolled in even calendar months) will receive a systemic loading dose of heparin of 15 units per kilogram of weight* by rapid (\< 10 seconds) intravenous bolus. The heparin concentration for the rapid intravenous loading bolus for this arm is also 1000 units per mL. Then a maintenance rate of heparin of 7.5 U/Kg per hour will be started and delivered via a syringe on the Prismaflex® proximal to the dialysis filter. The concentration of heparin used will be 1,000 units of heparin per mL of 0.9% NaCl.
Dose monitoring and adjustment: aPTT tests will be measured at baseline and at regular intervals thereafter. Adjustment of the heparin dose will be made using a heparin nomogram (see below) if the aPTT is not at the target level of greater than 35 seconds and less than 50 seconds. aPTT levels will be monitored every six hours routinely. If a significant change is made to the heparin infusion rate due to a prolonged aPTT, the aPTT will be checked at a shorter interval of three hours to ensure that aPTT is not persistently at a supratherapeutic level as this could increase risk for bleeding complications.
Nomogram for heparin infusion:
aPTT (in seconds)\< 35, infusion (continue), infusion rate change (increase 10%), repeat aPTT (in 6 hours);
aPTT (in seconds) 35 to 50, infusion (continue), infusion rate change (no change), repeat aPTT (in 6 hours);
aPTT (in seconds) 51 to 60, infusion (stop for 1/2 hour), infusion rate change (decrease 10%), repeat aPTT (in 3 hours);
aPTT (in seconds) 61 to 70, infusion (stop for 1 hour), infusion rate change (decrease 20%), repeat aPTT (in 3 hours);
aPTT (in seconds) 71 to 80, infusion (stop for 1.5 hours), infusion rate change (decrease 20%), repeat aPTT (in 3 hours);
aPTT (in seconds) >80, infusion (stop for 2 hours), infusion rate change (decrease 20%), repeat aPTT (in 3 hours);
For the purposes of this study, data will only be collected from the first filter used during the CVVHD treatment. Following the end of the study enrollment period patients will continue on CVVHD and heparin infusions at the discretion of their treating physicians. Heparin infusions will continue to be adjusted based on the heparin nomogram.
1,595 studies on the registry are indexed under Acute Kidney Injury; 371 are open to participants now.
This study's enrollment of 12 is below the median of 100 across 763 interventional studies indexed under Acute Kidney Injury.
Browse Acute Kidney Injury studies →Vanderbilt University is the lead sponsor of 508 studies on the registry; 19 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 5 (71%) have results posted.
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Exclusion Criteria:
Arm A will receive dilute heparin delivered as an intravenous infusion proximal to the dialysis filter.
Drug: Dilute unfractionated 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 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
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
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.
Time frame: 72 hours
Number of Major Bleeding Complications
Information on major bleeding complications, and need for blood product transfusions will be collected.
Time frame: 72 hours
| Milestone | Dilute Heparin | Standard Concentrated Heparin |
|---|---|---|
| Started | 4 | 8 |
| Completed | 3 | 4 |
| Not completed | 1 | 4 |
| Withdrew: Physician decision | 1 | 1 |
| Withdrew: Crrt stopped for head ct | 0 | 1 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Crrt stopped for head mri | 0 | 1 |
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.
| hours | Dilute Heparin | Standard Concentrated Heparin |
|---|---|---|
| Filter Life | 22.46 ± 3.32 | 33 ± 22.22 |
Information on major bleeding complications, and need for blood product transfusions will be collected.
| clinical active major bleeding episodes | Dilute Heparin | Standard Concentrated Heparin |
|---|---|---|
| Number of Major Bleeding Complications | 0 | 0 |
Collected over 72 hours from start of dialysis. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dilute Heparin | 2/4 (50%) | 0/4 (0%) | 0/4 (0%) |
| Standard Concentrated Heparin | 4/8 (50%) | 0/8 (0%) | 0/8 (0%) |
| Age, Continuous(years) | Dilute Heparin | Standard Concentrated Heparin | Total |
|---|---|---|---|
| Mean | 58.25 ± 16.5 | 57.5 ± 11 | 57.75 ± 12.75 |
| Sex: Female, Male(Participants) | Dilute Heparin | Standard Concentrated Heparin | Total |
|---|---|---|---|
| Female | 2 | 4 | 6 |
| Male | 2 | 4 | 6 |
| Region of Enrollment(participants) | Dilute Heparin | Standard Concentrated Heparin | Total |
|---|---|---|---|
| United States | 4 | 8 | 12 |
This study is terminated, as verified in Feb 2019. You cannot join it, but the record below documents what was studied.
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