Nafamostat Efficacy and Safety in Critically Ill Patients(NICE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Seoul National University Hospital
Sponsor:
Collaborator:
SK Chemicals Co.,Ltd.
Information provided by (Responsible Party):
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01486485
First received: December 2, 2011
Last updated: February 18, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Acute Kidney Injury
Drug: heparinized saline priming group
Drug: nafamostat infusion after heparinized saline priming
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Circuit Survival and Efficacy for Middle Molecular-weight Solute Elimination Between Nafamostat Infusion and Heparinized Saline Priming

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • the time of 1st membrane exchange [ Time Frame: the time of 'filter is clotted' ] [ Designated as safety issue: No ]
    the time of 'filter is clotted'


Secondary Outcome Measures:
  • Clearance of small molecule (urea) [ Time Frame: 0, 1, 6, 24h ] [ Designated as safety issue: No ]
    Clearance of small molecule (urea)

  • Clearance of middle molecule (β-2 microglobulin) [ Time Frame: 0, 1, 6, 24h ] [ Designated as safety issue: No ]
    Clearance of middle molecule (β-2 microglobulin)

  • ACT(activated coagulation time) measurements after 1hr of the CRRT [ Time Frame: after 1hr of the CRRT ] [ Designated as safety issue: No ]
    ACT(activated coagulation time) measurements after 1hr of the CRRT

  • Hemorrhagic complication [ Time Frame: during CRRT ] [ Designated as safety issue: No ]
    Hemorrhagic complication


Estimated Enrollment: 160
Study Start Date: March 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   20 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Injury stage of RIFLE criteria or more: > 2-fold increase in the serum creatinine or urine output < 0.5 mL/kg/hr for 12 hours
  2. Patients with any dialysis treatment before admission to the ICU or patients with end-stage renal failure and receiving dialysis
  3. Informed consent has been obtained.

Exclusion Criteria:

  1. patient age < 20 years or > 85 years
  2. life expectancy less than 3 months (ex. terminal stage of malignancy)
  3. Child-Pugh class C liver cirrhosis
  4. pregnancy or lactation
  5. history of anticoagulation prior to the randomization
  6. bleeding tendency (platelet count < 50,000/ul, INR > 2.5, PTT > 65, or fibrinogen < 1.00 g/L)
  7. history of hemorrhagic disease (ex. GI bleeding, cerebral hemorrhage, pulmonary hemorrhage)
  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: NCT01486485

Contacts
Contact: Dong Ki Kim, MD, PhD. 82-2-2072-2303 dkkim73@gmail.com

Locations
Korea, Republic of
National Health Insurance Corporation Ilsan Hospital Recruiting
Koyang, Korea, Republic of
Contact: Tae Ik Chang, MD    82-31-900-0246    tichang@hanmail.net   
Seoul National University Bundang Hospital Recruiting
Seongnam, Korea, Republic of
Contact: Sejoong Kim, MD, PhD    82-11-9196-5245    imsejoong@hanmail.net   
Seoul National University Boramae Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Jung Pyo Lee, MD, PhD    82-2-870-2261    kjwa1@medimail.co.kr   
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Su Mi Lee    82-2-2072-1705    promise131@hanmail.net   
Sponsors and Collaborators
Seoul National University Hospital
SK Chemicals Co.,Ltd.
Investigators
Study Chair: Dong Ki Kim, MD, PhD Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01486485     History of Changes
Other Study ID Numbers: Nafamostat01
Study First Received: December 2, 2011
Last Updated: February 18, 2013
Health Authority: South Korea: Institutional Review Board

Keywords provided by Seoul National University Hospital:
renal replacement therapy

Additional relevant MeSH terms:
Acute Kidney Injury
Wounds and Injuries
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Nafamostat
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Anticoagulants
Hematologic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 26, 2014