Last reviewed · How we verify

NCT04997265: SAFE-ECMO

Strategies for Anticoagulation During Venovenous ECMO

Completed NA Results posted Last updated 18 June 2025
What this trial tests

NA trial testing Low intensity anticoagulation in Acute Hypoxemic Respiratory Failure in 26 participants. Completed in 10 January 2024.

Timeline
12 May 2022
Primary endpoint
10 January 2024
10 January 2024

Quick facts

Lead sponsorVanderbilt University Medical Center
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment26
Start date12 May 2022
Primary completion10 January 2024
Estimated completion10 January 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Vanderbilt University Medical Center

Who can join

18 and older, any sex, with Acute Hypoxemic Respiratory Failure or Anticoagulant-induced Bleeding. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Major Bleeding Events Primary · From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.

Major bleeding event, according to the International Society on Thrombosis and Hemostasis, defined as: 1. Fatal bleeding 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome 3. Clinically overt bleeding associated with either a drop in hemoglobin level by at least 2.0 grams/dL or leading to transfusion of two or more units of packed red blood cells

GroupValue95% CI
Low Intensity Anticoagulation1
Moderate Intensity Anticoagulation4
Number of Participants With Thromboembolic Events Primary · From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.

Thromboembolic event defined as: 1. Deep venous thrombosis (DVT) 2. Acute pulmonary embolism (PE) 3. Intra-cardiac thrombosis 4. Ischemic stroke 5. Acute circuit thrombosis requiring urgent circuit exchange 6. Acute arterial thromboembolism

GroupValue95% CI
Moderate-intensity Anticoagulation0
Low-intensity Anticoagulation1
Number of Participants With Cannula-associated Deep Vein Thrombosis Secondary · 24-72 hours after decannulation

Cannula-associated deep vein thrombosis, as measured by four-extremity venous ultrasounds obtained 24-72 hours following decannulation among patients who were decannulation

GroupValue95% CI
Moderate-intensity Anticoagulation7
Low-intensity Anticoagulation5
Number of Circuit or Circuit Component Exchanges Secondary · From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days

Circuit or circuit component exchange during ECMO support

GroupValue95% CI
Moderate-intensity Anticoagulation2
Low-intensity Anticoagulation1
New Heparin Induced Thrombocytopenia Diagnosis Secondary · From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days

New diagnosis of Heparin Induced Thrombocytopenia as measured by clinically obtained serotonin release assay

GroupValue95% CI
Moderate-intensity Anticoagulation0
Low-intensity Anticoagulation0
Lowest Platelet Count Secondary · From randomization to the the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days

Lowest clinically obtained platelet count

GroupValue95% CI
Moderate-intensity Anticoagulation8870 – 132
Low-intensity Anticoagulation130115 – 170
Highest Total Bilirubin Values Secondary · From randomization to the the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days

Highest clinically obtained total bilirubin values

GroupValue95% CI
Low Intensity Anticoagulation1.20.6 – 1.4
Moderate Intensity Anticoagulation0.90.7 – 2.1
Highest Lactate Dehydrogenase Value Secondary · From randomization to the the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days

Highest clinically obtained lactate dehydrogenase value

GroupValue95% CI
Moderate-intensity Anticoagulation492426 – 543
Low-intensity Anticoagulation711320 – 941
Death Attributable to a Major Bleeding Event Secondary · From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days

In-hospital mortality attributable to a major bleeding event

GroupValue95% CI
Moderate-intensity Anticoagulation0
Low-intensity Anticoagulation0
Death Attributable to a Thromboembolic Event Secondary · From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days

In-hospital mortality attributable to a thromboembolic event

GroupValue95% CI
Moderate-intensity Anticoagulation0
Low-intensity Anticoagulation0
Ventilator-free Days Secondary · From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days

Number of days alive and free from mechanical ventilation between randomization and day 28.

GroupValue95% CI
Moderate-intensity Anticoagulation5430 – 57
Low-intensity Anticoagulation4739 – 56
ICU Length of Stay Secondary · From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days

Number of days in the ICU following randomization.

GroupValue95% CI
Moderate-intensity Anticoagulation116 – 20
Low-intensity Anticoagulation157 – 25

Sponsor's own description

Moderate intensity titrated dose anticoagulation has been used in patients receiving extracorporeal membrane oxygenation (ECMO) to prevent thromboembolism and thrombotic mechanical complications. As technology has improved, however, the incidence of thromboembolic events has decreased, leading to re-evaluation of the risks of anticoagulation, particularly during venovenous (V-V) ECMO. Recent data suggest that bleeding complications during V-V ECMO may be more strongly associated with mortality than thromboembolic complications, and case series have suggested that V-V ECMO can be safely performed without moderate or high intensity anticoagulation. At present, there is significant variability between institutions in the approach to anticoagulation during V-V ECMO. A definitive randomized controlled trial is needed to compare the effects of a low intensity fixed dose anticoagulation (low intensity) versus moderate intensity titrated dose anticoagulation (moderate intensity) on clinical outcomes during V-V ECMO. Before such a trial can be conducted, however, additional data are needed to inform the feasibility of the future trial.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Association of aPTT-Guided Anticoagulation Monitoring with Thromboembolic Events in Patients Receiving V-A ECMO Support: A Systematic Review and Meta-Analysis.
    Rajsic S, Breitkopf R, Treml B, Jadzic D, et al · · 2023 · cited 14× · PMID 37176673 · DOI 10.3390/jcm12093224
  2. Between a rock and a hard place: anticoagulation management for ECMO.
    Buchtele N, Levy JH. · · 2024 · cited 5× · PMID 38457000 · DOI 10.1007/s00063-024-01116-0
  3. Low-Intensity vs Moderate-Intensity Anticoagulation for Venovenous Extracorporeal Membrane Oxygenation: The Strategies for Anticoagulation During Venovenous Extracorporeal Membrane Oxygenation Pilot Trial.
    Gannon WD, Pratt EH, Vogelsong MA, Adkisson WH, et al · · 2025 · cited 2× · PMID 40081660 · DOI 10.1016/j.chest.2025.02.032
  4. Mortality and complications in low-dose vs standard-dose unfractionated heparin anticoagulation for extracorporeal membrane oxygenation: a systematic review and meta-analysis.
    Ng WW, Hui RW, Leung KC, Ng PY, et al · · 2026 · cited 1× · PMID 41552749 · DOI 10.1016/j.rpth.2025.102732
  5. Reply to Wendel-Garcia <i>et al</i>.: Low-Dose Anticoagulation to Prevent Intracranial Hemorrhage in COVID-19 Patients under Extracorporeal Membrane Oxygenation Support.
    Giani M, Schmidt M, Brodie D, Lorusso R, et al · · 2024 · PMID 38306656 · DOI 10.1164/rccm.202312-2295le

Verify or expand the search:

Other recruiting trials for Acute Hypoxemic Respiratory Failure

Currently open trials in the same condition.

Other Vanderbilt University Medical Center trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04997265.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing