Acute Hypoxemic Respiratory FailureSAFE-ECMONCT04997265
Strategies for Anticoagulation During Venovenous ECMO
A study testing Low intensity anticoagulation and Moderate Intensity Anticoagulation in people with Acute Hypoxemic Respiratory Failure and Anticoagulant-induced Bleeding, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
Moderate intensity titrated dose anticoagulation has been used in patients receiving extracorporeal membrane oxygenation (ECMO) to prevent thromboembolism and thrombotic mechanical complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure, Anticoagulant-induced Bleeding, Thromboembolism
- What is being tested?
- Low intensity anticoagulation and Moderate Intensity Anticoagulation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2022to 10 Jan 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient receiving V-V ECMO
- Patient is located in a participating unit of the Vanderbilt University Medical Center (VUMC) adult hospital.
Who cannot join
- Patient is pregnant
- Patient is a prisoner
- Patient is < 18 years old
- Patient underwent ECMO cannulation greater than 24 hours prior to screening
- Presence of an indication for systemic anticoagulation:
- Ongoing receipt of systemic anticoagulation
Show all 17Show fewer
- Planned administration of anticoagulation for an indication other than ECMO
- Presence of or plan to insert an arterial ECMO cannula
- Presence of a contraindication to anticoagulation:
- Active bleeding determined by treating clinicians to make anticoagulation unsafe
- Major surgery or trauma less than 72 hours prior to randomization
- Known history of a bleeding diathesis
- Ongoing severe thrombocytopenia (platelet count < 30,000)
- History of heparin-induced thrombocytopenia (HIT)
- Heparin allergy
- Positive SARS-CoV-2 test within prior 21 days or high clinical suspicion for COVID-19
- The treating clinician determines that the patient's risks of thromboembolism or bleeding necessitate a specific approach to anticoagulation management during V-V ECMO
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37209
About this study
Official title: Strategies for Anticoagulation During Venovenous ECMO: The SAFE-ECMO Pilot Trial
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.
Read the detailed description
Since the inception of Extracorporeal Membrane Oxygenation (ECMO), moderate intensity titrated dose anticoagulation has been used to prevent clinically harmful thromboembolism and thrombotic mechanical complications. The impact of thromboembolic events on clinical outcomes during venovenous (V-V) extracorporeal membrane oxygenation (ECMO), however, is unclear, and complications related to bleeding are common and associated with increased morbidity and mortality. These findings have led many experts to suggest that anticoagulation strategies during V-V ECMO should be re-evaluated.
Critical illness, in general, is associated with both coagulopathy and impaired hemostasis. These problems are compounded during ECMO by the artificial interface between blood and the non-biologic surface of the circuit components, which leads to activation of the coagulation system, consumptive thrombocytopenia, fibrinolysis, and thrombin generation. The sheer stress on blood components during ECMO also lead to destruction of high-molecular-weight von Willebrand multimers, interrupting primary hemostasis.
Both bleeding and thromboembolism are common complications during ECMO. Bleeding events have been associated with poor clinical outcomes, likely mediated by an increased incidence of intracranial hemorrhage during ECMO. During intra-operative cardiopulmonary bypass and venoarterial (V-A) ECMO, ischemic strokes are a common and potentially deadly complication. During V-V ECMO, however, the majority of thromboembolic events are cannula-associated DVT and circuit thromboses requiring exchange, which are of unclear clinical significance.
Various anticoagulation strategies have been proposed to balance the risks of bleeding and thromboembolism during V-V ECMO, including high intensity anticoagulation, moderate intensity anticoagulation, and low intensity anticoagulation (the equivalent of DVT prophylaxis). Observational studies have suggested that, compared to moderate intensity anticoagulation, low intensity anticoagulation reduces transfusion requirements without affecting the incidence of thrombosis, hemorrhage, or death. In one case series of 60 patients who were treated with only low-intensity subcutaneous heparin during V-V ECMO, rates of transfusions were lower than historical controls without any effect on the rate of thrombotic events. Similarly, a recent systematic review suggested that the rates of thromboembolism and circuit thrombosis among patients managed with a moderate intensity anticoagulation strategy during V-V ECMO were comparable to the rates reported among patients managed with a less intense anticoagulation strategy.
To date, there are no randomized controlled trials comparing low intensity to moderate intensity anticoagulation during V-V ECMO. Guidelines from the Extracorporeal Life Support Organization (ELSO), the pre-eminent group for ECMO education and research, provide little guidance for the selection of anticoagulation strategy, and anticoagulation practices are highly variable across institutions. A large, multicenter, randomized trial is needed to determine the ideal strategy to anticoagulation during V-V ECMO. Before such a trial can be conducted, however, additional data are needed on the feasibility of randomizing patients to a specific anticoagulation strategy and study measurements.
To facilitate a large, multicenter randomized controlled trial comparing low intensity anticoagulation to moderate intensity anticoagulation during V-V ECMO, a pilot trial is needed to establish feasibility and the performance of the primary outcome measures.
Primary aim of the study: To demonstrate feasibility of a future large, multi-center randomized controlled trial comparing low intensity to moderate intensity anticoagulation among adults receiving V-V ECMO by demonstrating the ability to recruit and randomize participants, adhere to assigned anticoagulation strategy, and demonstrate adequate separation between groups in therapy delivered and intensity of anticoagulation achieved with the assigned anticoagulation strategies.
Secondary aim of the study: To define and estimate the frequency of the primary efficacy, primary safety, and secondary outcomes of a future large, multi-center randomized controlled trial comparing low intensity vs moderate intensity anticoagulation among adults receiving V-V ECMO.
- Being tested
- Low intensity anticoagulation, Moderate Intensity Anticoagulation
- Keywords
- ARDS, Hypoxemic respiratory failure, Extracorporeal Membrane Oxygenation
- Medical subject headings
- Respiratory Insufficiency, Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low intensity anticoagulationOther
Participants assigned to the low intensity anticoagulation strategy will receive anticoagulation at doses used for DVT prophylaxis in critically ill patients. The choice of agent (e.g. heparin or enoxaparin) and specific dosing will be at the discretion of the treating clinicians and will be prospectively recorded.
Moderate Intensity AnticoagulationOther
Patients assigned to the moderate intensity anticoagulation strategy will receive anticoagulation targeting a PTT goal of 40-60 seconds or anti-Xa level of 0.2 to 0.3 IU/mL. Choice of anticoagulant and monitoring strategy (PTT or anti-Xa level) will be at the discretion of the treating clinicians and will be prospectively recorded. Anticoagulant drips will be titrated according to institutional protocols. For patients who survive to decannulation, the infusion will be stopped one hour prior to decannulation.
This approach to anticoagulation reflects the current approach for patients receiving V-V ECMO at Vanderbilt University Medical Center and is similar to protocols widely adopted for patients receiving V-V ECMO at other centers.
| Study group | Role | What they receive |
|---|---|---|
| Low Intensity Anticoagulation | Experimental | For patients assigned to the low intensity anticoagulation strategy, clinical teams will be instructed to initiate low intensity anticoagulation at doses and frequencies commonly used for deep vein thrombosis (DVT) prophylaxis. The choice of anticoagulant, dose, and frequency of administration will be deferred to treating clinicians. Receives: Other: Low intensity anticoagulation |
| Moderate Intensity Anticoagulation | Active comparator | For patients assigned to the moderate intensity anticoagulation group, clinical teams will be instructed to initiate a continuous infusion of moderate intensity anticoagulation targeting either a partial thromboplastin time (PTT) of 40-60 seconds or an Anti-Xa level of 0.2 to 0.3 IU/mL. The choice of anticoagulant and approach to dosing will be deferred to treating clinicians. Receives: Other: Moderate Intensity Anticoagulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Major Bleeding Events
Major bleeding event, according to the International Society on Thrombosis and Hemostasis, defined as:
- Fatal bleeding
- Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome
- 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
Measured: From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.
Number of Participants With Thromboembolic Events
Thromboembolic event defined as:
- Deep venous thrombosis (DVT)
- Acute pulmonary embolism (PE)
- Intra-cardiac thrombosis
- Ischemic stroke
- Acute circuit thrombosis requiring urgent circuit exchange
- Acute arterial thromboembolism
Measured: From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.
Secondary outcomes (12)
Number of Participants With Cannula-associated Deep Vein Thrombosis
Cannula-associated deep vein thrombosis, as measured by four-extremity venous ultrasounds obtained 24-72 hours following decannulation among patients who were decannulation
Measured: 24-72 hours after decannulation
Number of Circuit or Circuit Component Exchanges
Circuit or circuit component exchange during ECMO support
Measured: From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days
New Heparin Induced Thrombocytopenia Diagnosis
New diagnosis of Heparin Induced Thrombocytopenia as measured by clinically obtained serotonin release assay
Measured: From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days
Lowest Platelet Count
Lowest clinically obtained platelet count
Measured: 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 Total Bilirubin Values
Highest clinically obtained total bilirubin values
Measured: 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 Lactate Dehydrogenase Value
Highest clinically obtained lactate dehydrogenase value
Measured: 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
Death Attributable to a Major Bleeding Event
In-hospital mortality attributable to a major bleeding event
Measured: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Death Attributable to a Thromboembolic Event
In-hospital mortality attributable to a thromboembolic event
Measured: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Ventilator-free Days
Number of days alive and free from mechanical ventilation between randomization and day 28.
Measured: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
ICU Length of Stay
Number of days in the ICU following randomization.
Measured: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Hospital Length of Stay
Number of days in the hospital following randomization
Measured: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
In-hospital Mortality
Death prior to hospital discharge
Measured: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2021
- Study start12 May 2022
- Primary completion10 Jan 2024
- Study completion10 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Acute Hypoxemic Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single center, open-label, parallel-group, randomized pilot trial
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Whitney Gannon, Vanderbilt University Medical Center
- Investigators
- Jonathan D Casey, MD, MSc, Study director, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04997265
- Sponsor's protocol ID
- 202210
- Acronym
- SAFE-ECMO
- Status last verified
- Jun 2025
- First submitted
- 23 Jul 2021
- Last updated
- 18 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Request will be reviewed by the study team and approval will be contingent upon the execution of a data use agreement.
Publications
Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
PubMed 15842354Aubron C, DePuydt J, Belon F, Bailey M, Schmidt M, Sheldrake J, Murphy D, Scheinkestel C, Cooper DJ, Capellier G, Pellegrino V, Pilcher D, McQuilten Z. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care. 2016 Dec;6(1):97. doi: 10.1186/s13613-016-0196-7. Epub 2016 Oct 6.
PubMed 27714705Aubron C, Cheng AC, Pilcher D, Leong T, Magrin G, Cooper DJ, Scheinkestel C, Pellegrino V. Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study. Crit Care. 2013 Apr 18;17(2):R73. doi: 10.1186/cc12681.
PubMed 23594433Zangrillo A, Landoni G, Biondi-Zoccai G, Greco M, Greco T, Frati G, Patroniti N, Antonelli M, Pesenti A, Pappalardo F. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc. 2013 Sep;15(3):172-8.
PubMed 23944202Combes A, Leprince P, Luyt CE, Bonnet N, Trouillet JL, Leger P, Pavie A, Chastre J. Outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med. 2008 May;36(5):1404-11. doi: 10.1097/CCM.0b013e31816f7cf7.
PubMed 18434909Munshi L, Walkey A, Goligher E, Pham T, Uleryk EM, Fan E. Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis. Lancet Respir Med. 2019 Feb;7(2):163-172. doi: 10.1016/S2213-2600(18)30452-1. Epub 2019 Jan 11.
PubMed 30642776Murphy DA, Hockings LE, Andrews RK, Aubron C, Gardiner EE, Pellegrino VA, Davis AK. Extracorporeal membrane oxygenation-hemostatic complications. Transfus Med Rev. 2015 Apr;29(2):90-101. doi: 10.1016/j.tmrv.2014.12.001. Epub 2014 Dec 18.
PubMed 25595476Chlebowski MM, Baltagi S, Carlson M, Levy JH, Spinella PC. Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO. Crit Care. 2020 Jan 20;24(1):19. doi: 10.1186/s13054-020-2726-9.
PubMed 31959232Saini A, Spinella PC. Management of anticoagulation and hemostasis for pediatric extracorporeal membrane oxygenation. Clin Lab Med. 2014 Sep;34(3):655-73. doi: 10.1016/j.cll.2014.06.014. Epub 2014 Jul 24.
PubMed 25168949Doyle AJ, Hunt BJ. Current Understanding of How Extracorporeal Membrane Oxygenators Activate Haemostasis and Other Blood Components. Front Med (Lausanne). 2018 Dec 12;5:352. doi: 10.3389/fmed.2018.00352. eCollection 2018.
PubMed 30619862Tauber H, Ott H, Streif W, Weigel G, Loacker L, Fritz J, Heinz A, Velik-Salchner C. Extracorporeal membrane oxygenation induces short-term loss of high-molecular-weight von Willebrand factor multimers. Anesth Analg. 2015 Apr;120(4):730-6. doi: 10.1213/ANE.0000000000000554.
PubMed 25565317Kasirajan V, Smedira NG, McCarthy JF, Casselman F, Boparai N, McCarthy PM. Risk factors for intracranial hemorrhage in adults on extracorporeal membrane oxygenation. Eur J Cardiothorac Surg. 1999 Apr;15(4):508-14. doi: 10.1016/s1010-7940(99)00061-5.
PubMed 10371130Menaker J, Tabatabai A, Rector R, Dolly K, Kufera J, Lee E, Kon Z, Sanchez P, Pham S, Herr DL, Mazzeffi M, Rabinowitz RP, O'Connor JV, Stein DM, Scalea TM. Incidence of Cannula-Associated Deep Vein Thrombosis After Veno-Venous Extracorporeal Membrane Oxygenation. ASAIO J. 2017 Sep/Oct;63(5):588-591. doi: 10.1097/MAT.0000000000000539.
PubMed 28857905Cooper E, Burns J, Retter A, Salt G, Camporota L, Meadows CI, Langrish CC, Wyncoll D, Glover G, Ioannou N, Daly K, Barrett NA. Prevalence of Venous Thrombosis Following Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Respiratory Failure. Crit Care Med. 2015 Dec;43(12):e581-4. doi: 10.1097/CCM.0000000000001277.
PubMed 26308437Esper SA, Welsby IJ, Subramaniam K, John Wallisch W, Levy JH, Waters JH, Triulzi DJ, Hayanga JWA, Schears GJ. Adult extracorporeal membrane oxygenation: an international survey of transfusion and anticoagulation techniques. Vox Sang. 2017 Jul;112(5):443-452. doi: 10.1111/vox.12514. Epub 2017 May 3.
PubMed 28466601
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Strategies for Anticoagulation During Venovenous ECMO: The SAFE-ECMO Pilot Trial
- ClinicalTrials.gov ID
- NCT04997265
- Acronym / sponsor ID
- SAFE-ECMO / 202210
- Keywords
- ARDS, Hypoxemic respiratory failure, Extracorporeal Membrane Oxygenation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 12 May 2022 (actual)
- Primary completion
- 10 Jan 2024 (actual)
- Study completion
- 10 Jan 2024 (actual)
- First posted
- 9 Aug 2021 (actual)
- Results
- Posted 18 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Since the inception of Extracorporeal Membrane Oxygenation (ECMO), moderate intensity titrated dose anticoagulation has been used to prevent clinically harmful thromboembolism and thrombotic mechanical complications. The impact of thromboembolic events on clinical outcomes during venovenous (V-V) extracorporeal membrane oxygenation (ECMO), however, is unclear, and complications related to bleeding are common and associated with increased morbidity and mortality. These findings have led many experts to suggest that anticoagulation strategies during V-V ECMO should be re-evaluated.
Critical illness, in general, is associated with both coagulopathy and impaired hemostasis. These problems are compounded during ECMO by the artificial interface between blood and the non-biologic surface of the circuit components, which leads to activation of the coagulation system, consumptive thrombocytopenia, fibrinolysis, and thrombin generation. The sheer stress on blood components during ECMO also lead to destruction of high-molecular-weight von Willebrand multimers, interrupting primary hemostasis.
Both bleeding and thromboembolism are common complications during ECMO. Bleeding events have been associated with poor clinical outcomes, likely mediated by an increased incidence of intracranial hemorrhage during ECMO. During intra-operative cardiopulmonary bypass and venoarterial (V-A) ECMO, ischemic strokes are a common and potentially deadly complication. During V-V ECMO, however, the majority of thromboembolic events are cannula-associated DVT and circuit thromboses requiring exchange, which are of unclear clinical significance.
Various anticoagulation strategies have been proposed to balance the risks of bleeding and thromboembolism during V-V ECMO, including high intensity anticoagulation, moderate intensity anticoagulation, and low intensity anticoagulation (the equivalent of DVT prophylaxis). Observational studies have suggested that, compared to moderate intensity anticoagulation, low intensity anticoagulation reduces transfusion requirements without affecting the incidence of thrombosis, hemorrhage, or death. In one case series of 60 patients who were treated with only low-intensity subcutaneous heparin during V-V ECMO, rates of transfusions were lower than historical controls without any effect on the rate of thrombotic events. Similarly, a recent systematic review suggested that the rates of thromboembolism and circuit thrombosis among patients managed with a moderate intensity anticoagulation strategy during V-V ECMO were comparable to the rates reported among patients managed with a less intense anticoagulation strategy.
To date, there are no randomized controlled trials comparing low intensity to moderate intensity anticoagulation during V-V ECMO. Guidelines from the Extracorporeal Life Support Organization (ELSO), the pre-eminent group for ECMO education and research, provide little guidance for the selection of anticoagulation strategy, and anticoagulation practices are highly variable across institutions. A large, multicenter, randomized trial is needed to determine the ideal strategy to anticoagulation during V-V ECMO. Before such a trial can be conducted, however, additional data are needed on the feasibility of randomizing patients to a specific anticoagulation strategy and study measurements.
To facilitate a large, multicenter randomized controlled trial comparing low intensity anticoagulation to moderate intensity anticoagulation during V-V ECMO, a pilot trial is needed to establish feasibility and the performance of the primary outcome measures.
Primary aim of the study: To demonstrate feasibility of a future large, multi-center randomized controlled trial comparing low intensity to moderate intensity anticoagulation among adults receiving V-V ECMO by demonstrating the ability to recruit and randomize participants, adhere to assigned anticoagulation strategy, and demonstrate adequate separation between groups in therapy delivered and intensity of anticoagulation achieved with the assigned anticoagulation strategies.
Secondary aim of the study: To define and estimate the frequency of the primary efficacy, primary safety, and secondary outcomes of a future large, multi-center randomized controlled trial comparing low intensity vs moderate intensity anticoagulation among adults receiving V-V ECMO.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Single center, open-label, parallel-group, randomized pilot trial
| Arm | Type | Receives |
|---|---|---|
| Low Intensity Anticoagulation | Experimental | Other: Low intensity anticoagulationFor patients assigned to the low intensity anticoagulation strategy, clinical teams will be instructed to initiate low intensity anticoagulation at doses and frequencies commonly used for deep vein thrombosis (DVT) prophylaxis. The choice of anticoagulant, dose, and frequency of administration will be deferred to treating clinicians. |
| Moderate Intensity Anticoagulation | Active comparator | Other: Moderate Intensity AnticoagulationFor patients assigned to the moderate intensity anticoagulation group, clinical teams will be instructed to initiate a continuous infusion of moderate intensity anticoagulation targeting either a partial thromboplastin time (PTT) of 40-60 seconds or an Anti-Xa level of 0.2 to 0.3 IU/mL. The choice of anticoagulant and approach to dosing will be deferred to treating clinicians. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient receiving V-V ECMO
- Patient is located in a participating unit of the Vanderbilt University Medical Center (VUMC) adult hospital.
Key exclusion criteria (17 listed)
- Patient is pregnant
- Patient is a prisoner
- Patient is < 18 years old
- Patient underwent ECMO cannulation greater than 24 hours prior to screening
- Presence of an indication for systemic anticoagulation:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low intensity anticoagulationParticipants assigned to the low intensity anticoagulation strategy will receive anticoagulation at doses used for DVT prophylaxis in critically ill patients. The choice of agent (e.g. heparin or enoxaparin) and specific dosing will be at the discretion of the treating clinicians and will be prospectively recorded. | Other | Low Intensity Anticoagulation |
| Moderate Intensity AnticoagulationPatients assigned to the moderate intensity anticoagulation strategy will receive anticoagulation targeting a PTT goal of 40-60 seconds or anti-Xa level of 0.2 to 0.3 IU/mL. Choice of anticoagulant and monitoring strategy (PTT or anti-Xa level) will be at the discretion of the treating clinicians and will be prospectively recorded. Anticoagulant drips will be titrated according to institutional protocols. For patients who survive to decannulation, the infusion will be stopped one hour prior to decannulation. This approach to anticoagulation reflects the current approach for patients receiving V-V ECMO at Vanderbilt University Medical Center and is similar to protocols widely adopted for patients receiving V-V ECMO at other centers. | Other | Moderate Intensity Anticoagulation |
Primary outcome
Number of Participants With Major Bleeding Events
Time frame: 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
Number of Participants With Thromboembolic Events
Time frame: 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
12 secondary outcomes
Number of Participants With Cannula-associated Deep Vein Thrombosis
Time frame: 24-72 hours after decannulation
Number of Circuit or Circuit Component Exchanges
Time frame: From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days
New Heparin Induced Thrombocytopenia Diagnosis
Time frame: From randomization to the date of death or decannulation, whichever came first, through study completion, up to 134 days
Lowest Platelet Count
Time frame: 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 Total Bilirubin Values
Time frame: 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 Lactate Dehydrogenase Value
Time frame: 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
Death Attributable to a Major Bleeding Event
Time frame: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Death Attributable to a Thromboembolic Event
Time frame: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Ventilator-free Days
Time frame: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
ICU Length of Stay
Time frame: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Hospital Length of Stay
Time frame: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
In-hospital Mortality
Time frame: From randomization to the date of death or discharge, whichever came first, through study completion, up to 134 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15842354Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
- Background: PubMed 27714705Aubron C, DePuydt J, Belon F, Bailey M, Schmidt M, Sheldrake J, Murphy D, Scheinkestel C, Cooper DJ, Capellier G, Pellegrino V, Pilcher D, McQuilten Z. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care. 2016 Dec;6(1):97. doi: 10.1186/s13613-016-0196-7. Epub 2016 Oct 6.
- Background: PubMed 23594433Aubron C, Cheng AC, Pilcher D, Leong T, Magrin G, Cooper DJ, Scheinkestel C, Pellegrino V. Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study. Crit Care. 2013 Apr 18;17(2):R73. doi: 10.1186/cc12681.
- Background: PubMed 23944202Zangrillo A, Landoni G, Biondi-Zoccai G, Greco M, Greco T, Frati G, Patroniti N, Antonelli M, Pesenti A, Pappalardo F. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc. 2013 Sep;15(3):172-8.
- Background: PubMed 18434909Combes A, Leprince P, Luyt CE, Bonnet N, Trouillet JL, Leger P, Pavie A, Chastre J. Outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med. 2008 May;36(5):1404-11. doi: 10.1097/CCM.0b013e31816f7cf7.
- Background: PubMed 30642776Munshi L, Walkey A, Goligher E, Pham T, Uleryk EM, Fan E. Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis. Lancet Respir Med. 2019 Feb;7(2):163-172. doi: 10.1016/S2213-2600(18)30452-1. Epub 2019 Jan 11.
- Background: PubMed 25595476Murphy DA, Hockings LE, Andrews RK, Aubron C, Gardiner EE, Pellegrino VA, Davis AK. Extracorporeal membrane oxygenation-hemostatic complications. Transfus Med Rev. 2015 Apr;29(2):90-101. doi: 10.1016/j.tmrv.2014.12.001. Epub 2014 Dec 18.
- Background: PubMed 31959232Chlebowski MM, Baltagi S, Carlson M, Levy JH, Spinella PC. Clinical controversies in anticoagulation monitoring and antithrombin supplementation for ECMO. Crit Care. 2020 Jan 20;24(1):19. doi: 10.1186/s13054-020-2726-9.
- Background: PubMed 25168949Saini A, Spinella PC. Management of anticoagulation and hemostasis for pediatric extracorporeal membrane oxygenation. Clin Lab Med. 2014 Sep;34(3):655-73. doi: 10.1016/j.cll.2014.06.014. Epub 2014 Jul 24.
- Background: PubMed 30619862Doyle AJ, Hunt BJ. Current Understanding of How Extracorporeal Membrane Oxygenators Activate Haemostasis and Other Blood Components. Front Med (Lausanne). 2018 Dec 12;5:352. doi: 10.3389/fmed.2018.00352. eCollection 2018.
- Background: PubMed 25565317Tauber H, Ott H, Streif W, Weigel G, Loacker L, Fritz J, Heinz A, Velik-Salchner C. Extracorporeal membrane oxygenation induces short-term loss of high-molecular-weight von Willebrand factor multimers. Anesth Analg. 2015 Apr;120(4):730-6. doi: 10.1213/ANE.0000000000000554.
- Background: PubMed 10371130Kasirajan V, Smedira NG, McCarthy JF, Casselman F, Boparai N, McCarthy PM. Risk factors for intracranial hemorrhage in adults on extracorporeal membrane oxygenation. Eur J Cardiothorac Surg. 1999 Apr;15(4):508-14. doi: 10.1016/s1010-7940(99)00061-5.
- Individual participant dataSharing planned: Yes. Request will be reviewed by the study team and approval will be contingent upon the execution of a data use agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan D Casey, MD, MSc study director
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low intensity anticoagulation and Moderate Intensity Anticoagulation in people with Acute Hypoxemic Respiratory Failure and Anticoagulant-induced Bleeding, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Major Bleeding Events (time frame: From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04997265, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2025.