Nafamostat Efficacy and Safety in Critically Ill Patients(NICE)
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|ClinicalTrials.gov Identifier: NCT01486485|
Recruitment Status : Unknown
Verified February 2013 by Seoul National University Hospital.
Recruitment status was: Recruiting
First Posted : December 6, 2011
Last Update Posted : February 20, 2013
Acute kidney injury (AKI) is a common and serious problem in critically ill patients, and is known to be an independent risk factor for mortality. Renal replacement therapy (RRT) is the mainstay of supportive treatment of patients with severe acute kidney injury. The goal of RRT is to achieve adequate correction of uremia, electrolyte abnormalities, and volume overload while ensuring good hemodynamic tolerance. The advantages of continuous renal replacement therapy (CRRT) are increased time-averaged dialysis dose, less hemodynamic instability, and possibly, removal of high molecular weight solutes, such as inflammatory cytokines. Solute removal can occur by several different mechanisms in CRRT. For relatively small solutes, the importance of diffusion and convection is emphasized, for solutes of larger molecular weight, the importance of convection and adsorption is emphasized. The ability of a specific CRRT to remove a certain solute is determined by membrane characteristics. But actual measurements of middle molecule clearance in large clinical trials have not been available in most trials.
During CRRT, blood is conducted through an extracorporeal circuit, circuit clotting is a major problem in daily practice of CRRT, increasing blood loss, workload, and costs. Early clotting is related to bioincompatibility, critical illness, vascular access, CRRT circuit, and modality. Therefore, one major intervention to influence circuit survival is anticoagulation. However, systemic anticoagulation, usually with heparin, can produce hemorrhagic complications in patients at high risk of bleeding. To minimize the risk of bleeding, a number of alternative regimens has been proposed, however, each of those methods has its own limitations and complication. Nafamostat mesilate, a serine proteinase inhibitor, while inhibiting various clotting factors in filter circuit, is characterized by short half life resulting in little systemic anticoagulation effect. A recently developed CRRT AN69ST membrane® (Gambro Inc) is coated with a polyethylene imine (PEI, cationic biopolymer) on the membrane surface. Once adsorbed onto the membrane, heparin keeps its anticoagulant properties. Therefore CRRT has been managed without systemic administration of heparin.
The investigators will conduct a multicenter prospective randomized controlled open-label trial which compares the difference in circuit survival between between nafamostat infusion and heparinized saline priming as anticoagulation for CRRT. The primary end-point of this study is circuit survival, the time of 1st membrane exchange. The secondary end-point is clearance of small molecule (urea) and middle molecule (β2 microglobulin) at 0, 1, 6, 24h, ACT(activated coagulation time) measurements after 1hr of the CRRT, Hemorrhagic complication. This is a noninferiority trial. The aim is to demonstrate that nafamostat infusion is not inferior to the heparinized saline priming. For this purpose, at least 80 subjects (a total of 160) would be required for each group if type I error rate is 5% and type II error is 20% given 20% of drop-out rate during the study period. Block randomization will be used by means of a dedicated website.
There are still conflicting data on the effective exchange time of circuit membrane. Our study may help to improve prognosis in patients with severe AKI.
|Condition or disease||Intervention/treatment||Phase|
|Acute Kidney Injury||Drug: heparinized saline priming group Drug: nafamostat infusion after heparinized saline priming||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||160 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Circuit Survival and Efficacy for Middle Molecular-weight Solute Elimination Between Nafamostat Infusion and Heparinized Saline Priming|
|Study Start Date :||March 2012|
|Estimated Primary Completion Date :||August 2013|
|Estimated Study Completion Date :||August 2013|
Experimental: heparinized saline priming group
Experimental group : heparinized saline priming group
Drug: heparinized saline priming group
Active Comparator: nafamostat infusion group after heparinized saline priming
active comparator : nafamostat infusion group after heparinized saline priming
Drug: nafamostat infusion after heparinized saline priming
- the time of 1st membrane exchange [ Time Frame: the time of 'filter is clotted' ]the time of 'filter is clotted'
- Clearance of small molecule (urea) [ Time Frame: 0, 1, 6, 24h ]Clearance of small molecule (urea)
- Clearance of middle molecule (β-2 microglobulin) [ Time Frame: 0, 1, 6, 24h ]Clearance of middle molecule (β-2 microglobulin)
- ACT(activated coagulation time) measurements after 1hr of the CRRT [ Time Frame: after 1hr of the CRRT ]ACT(activated coagulation time) measurements after 1hr of the CRRT
- Hemorrhagic complication [ Time Frame: during CRRT ]Hemorrhagic complication
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01486485
|Contact: Dong Ki Kim, MD, PhD.||firstname.lastname@example.org|
|Korea, Republic of|
|National Health Insurance Corporation Ilsan Hospital||Recruiting|
|Koyang, Korea, Republic of|
|Contact: Tae Ik Chang, MD 82-31-900-0246 email@example.com|
|Seoul National University Bundang Hospital||Recruiting|
|Seongnam, Korea, Republic of|
|Contact: Sejoong Kim, MD, PhD 82-11-9196-5245 firstname.lastname@example.org|
|Seoul National University Boramae Medical Center||Recruiting|
|Seoul, Korea, Republic of|
|Contact: Jung Pyo Lee, MD, PhD 82-2-870-2261 email@example.com|
|Seoul National University Hospital||Recruiting|
|Seoul, Korea, Republic of|
|Contact: Su Mi Lee 82-2-2072-1705 firstname.lastname@example.org|
|Study Chair:||Dong Ki Kim, MD, PhD||Seoul National University Hospital|