The Effect of Prophylactic Anticoagulation on Major Bleeding Events in Hospitalized Chronic Kidney Disease and Lower Limb Fracture Patients.

NCT06795698 | Completed Phase 2

• 1 other identifier: 257/18
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

the risk of bleeding may be greater than the benefit of antithrombotic protection when prophylactically anticoagulating a patient with a lower limb fracture and advanced CKD. The primary objective was to evaluate the risk major bleeding in patients with lower limb fractures and advance CKD. The secondary objectives were to assess major bleeding in patients with lower limb fractures in CKD stage 4 and 5, thrombosis, death.

Conditions

Fractures, Bone; CKD Stage 4; CKD Stage 3; CKD Stage 5; Enoxaparin Adverse Reaction; Anticoagulant-induced Bleeding; Thromboses, Venous

Keywords

chronic kidney disease; anticoagulation; bleeding; bone fracture; thrombosis

Outcome Measures

Primary Outcomes (1)

• Major bleeding

  Number of Participants with Major bleeding were defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria (Schulman S). Defined as the composed event of: 1- Fatal bleeding, and/or; 2- Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or; 3- Bleeding causing a fall in hemoglobin level of 2.0 g/dL or more, or leading to transfusion of two or more units of whole blood or red cells

  From date of randomization until the date of first documented major bleeding or death from any cause, whichever came first up to 20 days. From date of randomization until surgery. Pre-intervention/procedure/surgery.

Secondary Outcomes (5)

• Thrombosis

  From date of randomization until the date of first documented thrombosis, or date of death from any cause, whichever came first, assessed from date of randomization until surgery up to 20 days. Pre-intervention/procedure/surgery.

• Dead

  through study completion, an average of 3 weeks

• number of transfusions

  From date of randomization until the date of first documented transfusions and number of transfusions. Pre-intervention/procedure/surgery.

• acute kidney injury

  From date of randomization until the date of first documented acute kidney injury up to 20 days. From date of randomization until surgery. Pre-intervention/procedure/surgery.

• hospitalization days

  number of days in hospital. through study completion, an average of 3 weeks

Study Arms (2)

Anticoagulation

ACTIVE COMPARATOR

The intervention drug of interest was prophylactic anticoagulation with enoxaparin 1mg/kg of ideal body weight subcutaneous every 24 hours in patients with eGFR \<30ml/min/1.73m2 (REF); enoxaparin will continue till surgery, any mandatory adverse event, dead or discharge. Enoxaparin or placebo started on admission to the trial, stopped 12 hours before surgery and all patients received prophylaxis anticoagulation restarted 6 to 12 hours postoperatively according to orthopedic surgeon practices. We choose enoxaparin, a low molecular weight heparin according to the ACCP guidelines as the gold standard for VTE prophylaxis in orthopedic patients

Drug: Enoxaparin

No anticoagulation

PLACEBO COMPARATOR

The no anticoagulation strategy was considerate the control group, we choose as placebo a bolus of 10ml normal saline 0.9%, was prepared and administered behind a screen or curtain, and the drug was administered through normal IV tubes

Drug: Enoxaparin

Interventions

Enoxaparin DRUG

enoxaparin 1mg/kg of ideal body weight subcutaneous every 24 hours in patients with eGFR \<30ml/min/1.73m2

Anticoagulation; No anticoagulation

Eligibility Criteria

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

You may qualify if:

• lower limb fracture before surgery
• CKD (chonic kidney disease)

You may not qualify if:

• \<18 years old
• kidney transplant
• hospital stay \<48 hours
• had received any anticoagulant before random assignment to a patient group
• had missing data that would render analysis incomplete

Sponsors & Collaborators

• Hospital Civil de Guadalajara: lead

Study Sites (1)

Hospital Civil de Guadalajara

Guadalajara, Jalisco, 44240, Mexico

Location

Related Publications (16)

• Lieberman JR, Bell JA. Venous Thromboembolic Prophylaxis After Total Hip and Knee Arthroplasty. J Bone Joint Surg Am. 2021 Aug 18;103(16):1556-1564. doi: 10.2106/JBJS.20.02250.

  PMID: 34133395 BACKGROUND

• Naylor KL, McArthur E, Leslie WD, Fraser LA, Jamal SA, Cadarette SM, Pouget JG, Lok CE, Hodsman AB, Adachi JD, Garg AX. The three-year incidence of fracture in chronic kidney disease. Kidney Int. 2014 Oct;86(4):810-8. doi: 10.1038/ki.2013.547. Epub 2014 Jan 15.

  PMID: 24429401 BACKGROUND

• Runesson B, Trevisan M, Iseri K, Qureshi AR, Lindholm B, Barany P, Elinder CG, Carrero JJ. Fractures and their sequelae in non-dialysis-dependent chronic kidney disease: the Stockholm CREAtinine Measurement project. Nephrol Dial Transplant. 2020 Nov 1;35(11):1908-1915. doi: 10.1093/ndt/gfz142.

  PMID: 31361316 BACKGROUND

• Kim SM, Long J, Montez-Rath M, Leonard M, Chertow GM. Hip Fracture in Patients With Non-Dialysis-Requiring Chronic Kidney Disease. J Bone Miner Res. 2016 Oct;31(10):1803-1809. doi: 10.1002/jbmr.2862. Epub 2016 Jul 11.

  PMID: 27145189 BACKGROUND

• Vilaca T, Salam S, Schini M, Harnan S, Sutton A, Poku E, Allen IE, Cummings SR, Eastell R. Risks of Hip and Nonvertebral Fractures in Patients With CKD G3a-G5D: A Systematic Review and Meta-analysis. Am J Kidney Dis. 2020 Oct;76(4):521-532. doi: 10.1053/j.ajkd.2020.02.450. Epub 2020 Jul 9.

  PMID: 32654892 BACKGROUND

• Isakova T, Cai X, Lee J, Mehta R, Zhang X, Yang W, Nessel L, Anderson AH, Lo J, Porter A, Nunes JW, Negrea L, Hamm L, Horwitz E, Chen J, Scialla JJ, de Boer IH, Leonard MB, Feldman HI, Wolf M; CRIC Study Investigators. Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2020 Feb;75(2):235-244. doi: 10.1053/j.ajkd.2019.07.022. Epub 2019 Oct 23.

  PMID: 31668375 BACKGROUND

• Burlacu A, Genovesi S, Goldsmith D, Rossignol P, Ortiz A, Kalra PA, Malyszko J, Banach M, Kanbay M, Covic A. Bleeding in advanced CKD patients on antithrombotic medication - A critical appraisal. Pharmacol Res. 2018 Mar;129:535-543. doi: 10.1016/j.phrs.2017.12.004. Epub 2017 Dec 5.

  PMID: 29208494 BACKGROUND

• Flevas DA, Megaloikonomos PD, Dimopoulos L, Mitsiokapa E, Koulouvaris P, Mavrogenis AF. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev. 2018 Apr 27;3(4):136-148. doi: 10.1302/2058-5241.3.170018. eCollection 2018 Apr.

  PMID: 29780621 BACKGROUND

• Reiss AB, Voloshyna I, De Leon J, Miyawaki N, Mattana J. Cholesterol Metabolism in CKD. Am J Kidney Dis. 2015 Dec;66(6):1071-82. doi: 10.1053/j.ajkd.2015.06.028. Epub 2015 Sep 1.

  PMID: 26337134 BACKGROUND

• Morris GK, Henry AP, Preston BJ. Prevention of deep-vein thrombosis by low-dose heparin in patients undergoing total hip replacement. Lancet. 1974 Oct 5;2(7884):797-800. doi: 10.1016/s0140-6736(74)91069-1. No abstract available.

  PMID: 4138248 BACKGROUND

• Pellegrini VD Jr, Clement D, Lush-Ehmann C, Keller GS, Evarts CM. The John Charnley Award. Natural history of thromboembolic disease after total hip arthroplasty. Clin Orthop Relat Res. 1996 Dec;(333):27-40.

  PMID: 8981880 BACKGROUND

• White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost. 2003 Sep;90(3):446-55. doi: 10.1160/TH03-03-0152.

  PMID: 12958614 BACKGROUND

• Santana DC, Emara AK, Orr MN, Klika AK, Higuera CA, Krebs VE, Molloy RM, Piuzzi NS. An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020. Medicina (Kaunas). 2020 Aug 19;56(9):416. doi: 10.3390/medicina56090416.

  PMID: 32824931 BACKGROUND

• Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, Samama CM. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e227S-e277S. doi: 10.1378/chest.11-2297.

  PMID: 22315263 BACKGROUND

• Douketis JD, Spyropoulos AC, Murad MH, Arcelus JI, Dager WE, Dunn AS, Fargo RA, Levy JH, Samama CM, Shah SH, Sherwood MW, Tafur AJ, Tang LV, Moores LK. Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline. Chest. 2022 Nov;162(5):e207-e243. doi: 10.1016/j.chest.2022.07.025. Epub 2022 Aug 11.

  PMID: 35964704 BACKGROUND

• Krauss ES, Segal A, Dengler N, Cronin M, Pettigrew J, Simonson BG. Utilization of the Caprini Score for Risk Stratification of the Arthroplasty Patient in the Prevention of Postoperative Venous Thrombosis. Semin Thromb Hemost. 2022 Jun;48(4):407-412. doi: 10.1055/s-0042-1742739. Epub 2022 Feb 28.

  PMID: 35226947 BACKGROUND

MeSH Terms

Conditions

Fractures, Bone; Renal Insufficiency, Chronic; Venous Thrombosis; Hemorrhage; Thrombosis

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Wounds and Injuries; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Blinding was achieved by shielding the patients from seeing the preparation of the study drug and having unblinded study personnel not involved in any study outcome assessments responsible for preparing and administering the study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of nephrology

Model Details: two groups recieved anticoagulation or placebo since randomization

Study Record Dates

• First Submitted: December 28, 2024
• First Posted: January 28, 2025
• Study Start: March 1, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: for 5 years
• Access Criteria: The files and data are in the physical and electronic archives of the Civil Hospital of Guadalajara Fray Antonio Alcalde and can be requested with prior authorization. All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

Locations

ME (1)