Comparison of Nafamostat and Unfractionated Heparin in RRT for Sepsis Associated AKI

NCT06375616 | Not Yet Recruiting Phase 4

• 1 other identifier: KY2024-023
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare the safety and efficacy of nafamostat mesylate (NM) and unfractionated heparin (UFH) in the process of renal replacement therapy (RRT) for patients suffering from sepsis associated acute kidney injury (SA-AKI). The main questions it aims to answer are: The impact of NM and UFH on platelet count in septic patients undergoing RRT treatment. The satisfaction with anticoagulation of NM and UFH in septic patients undergoing RRT treatment. The 28-day all-cause mortality rate of septic patients undergoing RRT treatment with NM and UFH. Researchers will use NM or UFH as anticoagulation during RRT in SA-AKI patients, assessing effects on platelet count, anticoagulation satisfaction, and mortality. Participants will receive NM or UFH as anticoagulation during RRT for a minimum of 7 days. Bleeding symptoms, platelet count and coagulation function will be monitored daily. Platelet changes during the 7-day treatment period and survival status at 28 days post-treatment will be recorded.

Conditions

Sepsis

Keywords

renal replacement therapy; acute kidney injury; nafamostat mesylate

Outcome Measures

Primary Outcomes (1)

• Platelet decline rate

  (baseline platelet count - day 7 platelet count)/baseline platelet count \*100%

  7 days after initiation of RRT treatment

Secondary Outcomes (1)

• Satisfaction of filter anticoagulation

  7 days after initiation of RRT treatment

Other Outcomes (1)

• All-cause mortality at 28 days

  28 days after initiation of RRT treatment

Study Arms (2)

Nafamostat

EXPERIMENTAL

Patients in NM arm will receive nafamostat mesylate as as anticoagulation during renal replacement therapy.

Drug: Nafamostat Mesylate

Heparin

ACTIVE COMPARATOR

Patients in UFH arm will receive unfractionated heparin as as anticoagulation during renal replacement therapy.

Drug: Unfractionated Heparin

Interventions

Nafamostat Mesylate DRUG

During RRT, a priming dose of 20 mg of nafamostat mesylate (NM) is administered before initiation of the procedure. Upon starting the machine, there is no loading dose, but a maintenance infusion rate of 25 mg/h of NM is maintained. NM is discontinued in the last half hour before the end of the RRT session.

Also known as: Nafamostat, Nafamostat Mesylate for Injection, NM

Nafamostat

Unfractionated Heparin DRUG

During RRT, a priming dose of 50 mg of unfractionated heparin (UFH) is administered before initiation of the procedure. Upon starting the machine, a loading dose of 0.2 mg/kg of UFH is given, followed by a maintenance infusion rate of 0.1 mg/kg/h of UFH. The anticoagulant is discontinued in the last half hour before the end of the RRT session.

Also known as: heparin, UFH

Heparin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 14 years old, and ≤ 90 years old.
• Sepsis or septic shock.
• AKI (Acute Kidney Injury), with stage of 2-3.
• Received renal replacement therapy (RRT) for ≥ 24 hours.
• Survival time ≥ 48 hours.

You may not qualify if:

• Presence of bleeding tendency or active bleeding.
• Pre-existing chronic kidney disease or already undergoing routine hemodialysis.
• With liver failure, severe hematologic disorders, malignancies, or other significant underlying diseases
• Pre-using of anticoagulant or antiplatelet medications such as aspirin, clopidogrel, rivaroxaban, dabigatran, or ticagrelor
• Allergy to heparin or nafamostat mesylate.
• Survival time \< 48 hours or RRT treatment time \< 24 hours.
• Initial platelet count \< 50 × 10\^9/L.
• Participation in another clinical trial within the past 1 month.

Sponsors & Collaborators

• Shen Lei: lead

Study Sites (1)

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Location

Related Publications (6)

• Zarbock A, Nadim MK, Pickkers P, Gomez H, Bell S, Joannidis M, Kashani K, Koyner JL, Pannu N, Meersch M, Reis T, Rimmele T, Bagshaw SM, Bellomo R, Cantaluppi V, Deep A, De Rosa S, Perez-Fernandez X, Husain-Syed F, Kane-Gill SL, Kelly Y, Mehta RL, Murray PT, Ostermann M, Prowle J, Ricci Z, See EJ, Schneider A, Soranno DE, Tolwani A, Villa G, Ronco C, Forni LG. Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup. Nat Rev Nephrol. 2023 Jun;19(6):401-417. doi: 10.1038/s41581-023-00683-3. Epub 2023 Feb 23.

  PMID: 36823168 BACKGROUND

• Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ. 2019 Jan 9;364:k4891. doi: 10.1136/bmj.k4891.

  PMID: 30626586 BACKGROUND

• Ohtake Y, Hirasawa H, Sugai T, Oda S, Shiga H, Matsuda K, Kitamura N. Nafamostat mesylate as anticoagulant in continuous hemofiltration and continuous hemodiafiltration. Contrib Nephrol. 1991;93:215-7. doi: 10.1159/000420222. No abstract available.

  PMID: 1666354 BACKGROUND

• Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten H, Ronco C, Kellum JA. Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators. Intensive Care Med. 2007 Sep;33(9):1563-70. doi: 10.1007/s00134-007-0754-4. Epub 2007 Jun 27.

  PMID: 17594074 BACKGROUND

• Maruyama Y, Yoshida H, Uchino S, Yokoyama K, Yamamoto H, Takinami M, Hosoya T. Nafamostat mesilate as an anticoagulant during continuous veno-venous hemodialysis: a three-year retrospective cohort study. Int J Artif Organs. 2011 Jul;34(7):571-6. doi: 10.5301/IJAO.2011.8535.

  PMID: 21786254 BACKGROUND

• Makino S, Egi M, Kita H, Miyatake Y, Kubota K, Mizobuchi S. Comparison of nafamostat mesilate and unfractionated heparin as anticoagulants during continuous renal replacement therapy. Int J Artif Organs. 2016 Jan;39(1):16-21. doi: 10.5301/ijao.5000465. Epub 2016 Feb 9.

  PMID: 26868216 BACKGROUND

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Interventions

nafamostat; Injections; Heparin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Lei Shen, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lei Shen, MD

CONTACT

86-021-52887920; sh_leisen@126.com

Yiqi Yu, MD

CONTACT

86-021-52887920; yyq19890619@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 19, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)