Prospective Observational Pilot Study of LMWH Versus UFH as ECMO Anticoagulation in Lung Transplantation

NCT06868823 | Recruiting

• 1 other identifier: EK-704-24
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this observational pilot study is to evaluate the effectiveness and safety of low-molecular-weight heparin (LMWH) compared to unfractionated heparin (UFH) as anticoagulation in perioperative ECMO during bilateral lung transplantation. The main question this study seeks to answer is: Does LMWH provide a safe and effective alternative to UFH for ECMO anticoagulation in lung transplantation, with reduced bleeding and thrombotic complications? Patients undergoing bilateral lung transplantation with perioperative veno-arterial (V-A) ECMO support will be assigned to one of two anticoagulation strategies: UFH group: Standard UFH anticoagulation monitored using ROTEM. LMWH group: Enoxaparin-based anticoagulation monitored using ROTEM. The study will assess perioperative blood loss, hemoglobin levels, transfusion needs, and thrombotic events. Additional analyses will include coagulation profile assessments using point-of-care (POC) tests, thrombin generation test (TGT), and laboratory coagulation parameters.

Conditions

Lung Transplantation; Extracorporeal Membrane Oxygenation (ECMO); Anticoagulants and Bleeding Disorders

Keywords

Lung Transplantation; Extracorporeal Membrane Oxygenation (ECMO); Anticoagulation; Low-Molecular-Weight Heparin (LMWH); Unfractionated Heparin (UFH); Thrombosis Prevention; Bleeding Complications; Coagulation Management in Surgery; Hemorrhagic and Thrombotic Events; Perioperative Hemostasis

Outcome Measures

Primary Outcomes (4)

• Perioperative Blood Loss

  Total volume of blood lost (milliliters, mL) during surgery, measured as the volume collected in suction canisters at the end of the operation, after subtracting irrigation fluids.

  Measured intraoperatively, at the end of surgery.

• Change in Hemoglobin Levels during surgery and within 24 hours after surgery

  The difference in hemoglobin levels (g/L) measured at baseline (preoperative) and at the end of surgery and between immediate postoperative levels and after 24 hours after surgery. This outcome evaluates the extent of perioperative blood loss and its impact on oxygen-carrying capacity.

  Intraoperative: Change in hemoglobin from preoperative levels to the end of surgery. Postoperative: Change in hemoglobin from preoperative levels to 24 hours post-surgery.

• Blood Transfusion Requirements during surgery and Within 24 Hours after surgery

  The total number of packed red blood cell (PRBC) units transfused to the patient intraoperatively and within the first 24 hours postoperatively. This outcome assesses the extent of blood loss and the need for transfusion support in ECMO-supported lung transplantation.

  Intraoperative: PRBC transfusions administered during surgery. Postoperative: PRBC transfusions administered within the first 24 hours after surgery.

• Incidence of Thrombotic Complications during surhery and within 24 Hours postoperatively.

  The number of thrombotic events occurring intraoperatively and within the first 24 hours postoperatively, including ECMO circuit thrombosis, deep vein thrombosis (DVT), arterial thrombosis, pulmonary embolism (PE), myocardial infarction (MI), and ischemic stroke (CVA). Thrombotic complications will be identified based on clinical signs, imaging studies, and laboratory results, including: ECMO circuit thrombosis requiring urgent ECMO replacement. Limb ischemia due to arterial or venous thrombosis. Deep vein thrombosis (DVT) with \>50% luminal obstruction, confirmed by ultrasound. Pulmonary embolism (PE) confirmed by CT pulmonary angiography. Myocardial infarction (MI) diagnosed based on electrocardiographic changes and cardiac biomarkers. Ischemic stroke (CVA) confirmed by neurological examination and brain imaging (CT/MRI).

  Intraoperative: Thrombotic events occurring during surgery. Postoperative: Thrombotic events occurring within 24 hours after surgery.

Secondary Outcomes (3)

• Coagulation Profile Assessed by Point-of-Care (POC) Tests

  Before anticoagulation administration; 5 minutes after anticoagulation; at ≥500 mL blood loss with ongoing bleeding "wet surgical field"; 5 minutes after NovoSeven (activated FVIIa); at end of surgery before ECMO explantation; upon ICU admission

• Coagulation Profile Assessed by Thrombin Generation Test (TGT)

  Before anticoagulation administration; 5 minutes after anticoagulation; at ≥500 mL blood loss with ongoing bleeding "wet surgical field"; 5 minutes after NovoSeven (activated FVIIa); at end of surgery before ECMO explantation; upon ICU admission

• Coagulation Profile Assessed by Standard Laboratory Tests

  Before anticoagulation administration; 5 minutes after anticoagulation; at ≥500 mL blood loss with ongoing bleeding "wet surgical field"; 5 minutes after NovoSeven (activated FVIIa); at end of surgery before ECMO explantation; upon ICU admission

Study Arms (2)

UFH Anticoagulation Group

Participants in this group will receive unfractionated heparin (UFH) as the standard anticoagulation regimen during perioperative veno-arterial (V-A) ECMO support for bilateral lung transplantation. UFH Administration: A bolus of 20-40 IU/kg UFH will be administered 30 minutes before ECMO initiation. Continuous UFH infusion of 2-6 mL/h (dilution: 100 mg/50 mL) will be maintained. Coagulation Monitoring: ROTEM (EXTEM, INTEM, HEPTEM, FIBTEM) will be used for real-time assessment. The target CT INTEM/CT HEPTEM ratio will be maintained at 1.2-1.5 to guide anticoagulation adjustments. Coagulation and Hemostasis Assessments: Standard laboratory coagulation tests (aPTT, PT, TT, fibrinogen, FXIII, D-dimers, anti-Xa, platelet count, hemoglobin, hematocrit) will be performed at predefined timepoints. Point-of-care (POC) testing and thrombin generation test (TGT) will be used for additional evaluation.

LMWH Anticoagulation Group

Participants in this group will receive low-molecular-weight heparin (LMWH) as an alternative anticoagulation strategy during perioperative veno-arterial (V-A) ECMO support for bilateral lung transplantation. LMWH Administration: A bolus of 20-40 IU/kg LMWH (Enoxaparin) will be administered 30 minutes before ECMO initiation. Continuous LMWH infusion of 2-6 mL/h (dilution: 100 mg/50 mL) will be maintained. Coagulation Monitoring: ROTEM (EXTEM, INTEM, HEPTEM, FIBTEM) will be used for real-time assessment. The CT INTEM/CT HEPTEM difference will be maintained at 20-30 seconds to guide anticoagulation adjustments. Coagulation and Hemostasis Assessments: Standard laboratory coagulation tests (aPTT, PT, TT, fibrinogen, FXIII, D-dimers, anti-Xa, platelet count, hemoglobin, hematocrit) will be performed at predefined timepoints. Point-of-care (POC) testing and thrombin generation test (TGT) will be used for additional evaluation.

Eligibility Criteria

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

Study Population

The study population will consist of patients indicated for bilateral lung transplantation from the Czech Republic and Slovakia, who will undergo surgery at Motol Hospital in Prague.

You may qualify if:

• ⃣ Adults (≥18 years old).
• ⃣ Patients undergoing bilateral lung transplantation with perioperative veno-arterial (V-A) ECMO support.
• ⃣ Planned perioperative anticoagulation with either UFH or LMWH, as determined by the attending anesthesiologist.
• ⃣ Ability to provide informed consent or consent provided by a legally authorized representative.

You may not qualify if:

• ⃣ Patients receiving ECMO as a bridge to lung transplantation.
• ⃣ Patients requiring postoperative continuation of ECMO.
• ⃣ Patients with perioperative blood loss ≥3,000 mL.
• ⃣ Patients undergoing lung re-transplantation.
• ⃣ History of severe coagulopathy or bleeding disorder.
• ⃣ Active use of antiplatelet or anticoagulant therapy (excluding study anticoagulants).
• ⃣ Known heparin-induced thrombocytopenia (HIT).
• ⃣ Severe liver dysfunction (Child-Pugh C) or end-stage renal disease requiring dialysis.
• ⃣ Pregnant or breastfeeding women.

Sponsors & Collaborators

• University Hospital, Motol: lead

Study Sites (1)

University Hospital Motol, 2nd Faculty of Medicine, Charles University in Prague and 3rd Department of Surgery, First Faculty of Medicine, Charles University, and Motol University Hospital, Lung Transplant Program

Prague, Czech Republic, 150 06, Czechia

RECRUITING

Related Publications (22)

• Lisman T, Adelmeijer J, Heijnen HF, de Groot PG. Recombinant factor VIIa restores aggregation of alphaIIbbeta3-deficient platelets via tissue factor-independent fibrin generation. Blood. 2004 Mar 1;103(5):1720-7. doi: 10.1182/blood-2003-07-2287. Epub 2003 Oct 30.

  PMID: 14592825 BACKGROUND

• Brase J, Finger B, He J, Wirtz K, Stun L, McMillen R, Flynn B. Analysis of Outcomes Using Low-Dose and Early Administration of Recombinant Activated Factor VII in Cardiac Surgery. Ann Thorac Surg. 2016 Jul;102(1):35-40. doi: 10.1016/j.athoracsur.2016.01.004. Epub 2016 Feb 10.

  PMID: 26874365 BACKGROUND

• Xiao Z, Theroux P. Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation. 1998 Jan 27;97(3):251-6. doi: 10.1161/01.cir.97.3.251.

  PMID: 9462526 BACKGROUND

• Burgess JK, Chong BH. The platelet proaggregating and potentiating effects of unfractionated heparin, low molecular weight heparin and heparinoid in intensive care patients and healthy controls. Eur J Haematol. 1997 Apr;58(4):279-85. doi: 10.1111/j.1600-0609.1997.tb01667.x.

  PMID: 9186540 BACKGROUND

• Ajayi AA, Pharmacols FB, Cooper J, Horn EH, Rubin PC. Comparison of the effects of unfractionated heparin and the low-molecular-weight heparins dalteparin and enoxaparin on spontaneous platelet aggregation and adenosine diphosphate activity in platelets during the third trimester of pregnancy. Methods Find Exp Clin Pharmacol. 2007 Oct;29(8):539-45. doi: 10.1358/mf.2007.29.8.1116308.

  PMID: 18040530 BACKGROUND

• Durila M, Vajter J, Garaj M, Berousek J, Lischke R, Hlavacek M, Vymazal T. Intravenous enoxaparin guided by anti-Xa in venovenous extracorporeal membrane oxygenation: A retrospective, single-center study. Artif Organs. 2025 Mar;49(3):486-496. doi: 10.1111/aor.14879. Epub 2024 Oct 3.

  PMID: 39360891 BACKGROUND

• Yassen KA, Refaat EK, Helal SM, Metwally AA, Youssef SD, Gorlinger K. Detection and quantification of perioperative heparin-like effects by rotational thromboelastometry in living-donor liver transplant recipients: A prospective observational study. J Anaesthesiol Clin Pharmacol. 2023 Apr-Jun;39(2):285-291. doi: 10.4103/joacp.joacp_521_21. Epub 2022 Jun 15.

  PMID: 37564856 BACKGROUND

• Rigal JC, Boissier E, Lakhal K, Riche VP, Durand-Zaleski I, Rozec B. Cost-effectiveness of point-of-care viscoelastic haemostatic assays in the management of bleeding during cardiac surgery: protocol for a prospective multicentre pragmatic study with stepped-wedge cluster randomised controlled design and 1-year follow-up (the IMOTEC study). BMJ Open. 2019 Nov 5;9(11):e029751. doi: 10.1136/bmjopen-2019-029751.

  PMID: 31694845 BACKGROUND

• Schaden E, Schober A, Hacker S, Spiss C, Chiari A, Kozek-Langenecker S. Determination of enoxaparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent. Blood Coagul Fibrinolysis. 2010 Apr;21(3):256-61. doi: 10.1097/MBC.0b013e328337014c.

  PMID: 20087172 BACKGROUND

• Ichikawa J, Kodaka M, Nishiyama K, Hirasaki Y, Ozaki M, Komori M. Reappearance of circulating heparin in whole blood heparin concentration-based management does not correlate with postoperative bleeding after cardiac surgery. J Cardiothorac Vasc Anesth. 2014 Aug;28(4):1003-7. doi: 10.1053/j.jvca.2013.10.010. Epub 2014 Feb 5.

  PMID: 24508375 BACKGROUND

• Durila M, Vajter J, Garaj M, Smetak T, Hedvicak P, Berousek J, Vymazal T. Acquired primary hemostasis pathology detected by platelet function analyzer 200 seen during extracorporeal membrane oxygenation is sufficient to prevent circuit thrombosis: A pilot study. J Heart Lung Transplant. 2020 Sep;39(9):980-982. doi: 10.1016/j.healun.2020.05.015. Epub 2020 Jun 11. No abstract available.

  PMID: 32591313 BACKGROUND

• Garaj M, Durila M, Vajter J, Solcova M, Marecek F, Hrachovinova I. Extracorporeal membrane oxygenation seems to induce impairment of primary hemostasis pathology as measured by a Multiplate analyzer: An observational retrospective study. Artif Organs. 2022 May;46(5):899-907. doi: 10.1111/aor.14142. Epub 2021 Dec 17.

  PMID: 34904233 BACKGROUND

• Garaj M, Francesconi A, Durila M, Vajter J, Holubova G, Hrachovinova I. ECMO produces very rapid changes in primary hemostasis detected by PFA-200 during lung transplantation: An observational study. J Heart Lung Transplant. 2024 Nov;43(11):1771-1776. doi: 10.1016/j.healun.2024.07.012. Epub 2024 Jul 20.

  PMID: 39038564 BACKGROUND

• Gratz J, Pausch A, Schaden E, Baierl A, Jaksch P, Erhart F, Hoetzenecker K, Wiegele M. Low molecular weight heparin versus unfractioned heparin for anticoagulation during perioperative extracorporeal membrane oxygenation: A single center experience in 102 lung transplant patients. Artif Organs. 2020 Jun;44(6):638-646. doi: 10.1111/aor.13642. Epub 2020 Feb 18.

  PMID: 31951030 BACKGROUND

• Lee YY, Baik HJ, Lee H, Kim CH, Chung RK, Han JI, Joo H, Woo JH. Heparin-free veno-venous extracorporeal membrane oxygenation in a multiple trauma patient: A case report. Medicine (Baltimore). 2020 Jan;99(5):e19070. doi: 10.1097/MD.0000000000019070.

  PMID: 32000456 BACKGROUND

• Chung M, Cabezas FR, Nunez JI, Kennedy KF, Rick K, Rycus P, Mehra MR, Garan AR, Kociol RD, Grandin EW. Hemocompatibility-Related Adverse Events and Survival on Venoarterial Extracorporeal Life Support: An ELSO Registry Analysis. JACC Heart Fail. 2020 Nov;8(11):892-902. doi: 10.1016/j.jchf.2020.09.004.

  PMID: 33121701 BACKGROUND

• Nunez JI, Gosling AF, O'Gara B, Kennedy KF, Rycus P, Abrams D, Brodie D, Shaefi S, Garan AR, Grandin EW. Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis. Intensive Care Med. 2022 Feb;48(2):213-224. doi: 10.1007/s00134-021-06593-x. Epub 2021 Dec 18.

  PMID: 34921625 BACKGROUND

• McMichael ABV, Ryerson LM, Ratano D, Fan E, Faraoni D, Annich GM. 2021 ELSO Adult and Pediatric Anticoagulation Guidelines. ASAIO J. 2022 Mar 1;68(3):303-310. doi: 10.1097/MAT.0000000000001652.

  PMID: 35080509 BACKGROUND

• Martin AK, Mercier O, Fritz AV, Gelzinis TA, Hoetzenecker K, Lindstedt S, Marczin N, Wilkey BJ, Schecter M, Lyster H, Sanchez M, Walsh J, Morrissey O, Levvey B, Landry C, Saatee S, Kotecha S, Behr J, Kukreja J, Dellgren G, Fessler J, Bottiger B, Wille K, Dave K, Nasir BS, Gomez-De-Antonio D, Cypel M, Reed AK. ISHLT Consensus Statement on the Perioperative use of ECLS in Lung Transplantation: Part II: Intraoperative Considerations. J Heart Lung Transplant. 2026 Jan;45(1):e35-e62. doi: 10.1016/j.healun.2024.08.027. Epub 2024 Oct 23.

  PMID: 39453286 BACKGROUND

• Zhou AL, Jennings MR, Akbar AF, Ruck JM, Oak A, Kalra A, Larson EL, Casillan AJ, Ha JS, Merlo CA, Bush EL. Utilization and outcomes of nonintubated extracorporeal membrane oxygenation as a bridge to lung transplant. J Heart Lung Transplant. 2025 Apr;44(4):661-669. doi: 10.1016/j.healun.2024.10.021. Epub 2024 Oct 30.

  PMID: 39486773 BACKGROUND

• Dhanani Z, Gupta R. The Management of Interstitial Lung Disease in the ICU: A Comprehensive Review. J Clin Med. 2024 Nov 6;13(22):6657. doi: 10.3390/jcm13226657.

  PMID: 39597801 BACKGROUND

• Basta MN. Severe Acute Respiratory Distress Syndrome in an Adult Patient With Human Metapneumovirus Infection Successfully Managed With Veno-Venous Extracorporeal Membrane Oxygenation. Semin Cardiothorac Vasc Anesth. 2025 Mar;29(1):74-81. doi: 10.1177/10892532241301195. Epub 2024 Nov 19.

  PMID: 39561244 BACKGROUND

MeSH Terms

Conditions

Hemostatic Disorders

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Miroslav Durila, prof. M.D., Ph.D., MHA

CONTACT

+420224435440; miroslav.durila@fnmoto.cz

Gabriela Holubova, M.D.

CONTACT

+420224435440; gabriela.holubova@fnmotol.cz

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. M.D. Miroslav Durila, Ph.D., MHA

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: March 11, 2025
• Study Start: May 1, 2025
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: from march 2025
• Access Criteria: contact me to by email

Locations

CZ (1)