Trial Outcomes & Findings for Strategies for Anticoagulation During Venovenous ECMO (NCT NCT04997265)

Results Overview

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

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

26 participants

Primary outcome timeframe

From randomization to the date of death or the date 24 hours after decannulation, whichever came first, through study completion, up to 134 days.

Results posted on

2025-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Moderate-intensity Anticoagulation Patients assigned to the moderate-intensity anticoagulation group received a continuous intravenous infusion of an anticoagulant targeting a goal aPTT of 40-60 seconds or a goal anti-Xa level of 0.2 to 0.3 IU/mL. The choice of anticoagulant (e.g., heparin or bivalirudin), monitoring strategy (e.g., partial thromboplastin time or anti-Xa level), frequency of monitoring, and protocol for titrating anticoagulation to achieve goals was determined by treating clinicians and institutional protocols. The protocols used to titrate continuous infusions of anticoagulation at each center are consistent with current recommendations and protocols for patients receiving venovenous ECMO in clinical care at other centers.	Low-intensity Anticoagulation Patients assigned to the low-intensity anticoagulation group received intermittent subcutaneous injections of an anticoagulant at a dose used for deep venous thromboembolism prophylaxis in critically ill patients. The choice of anticoagulant (e.g. heparin or enoxaparin) and the dose used for deep venous thromboembolism prophylaxis was determined by treating clinicians and institutional protocols.
Overall Study STARTED	14	12
Overall Study COMPLETED	14	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Strategies for Anticoagulation During Venovenous ECMO

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Intensity Anticoagulation n=12 Participants Low intensity anticoagulation: 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 Anticoagulation n=14 Participants Moderate Intensity Anticoagulation: Participants 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. 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.	Total n=26 Participants Total of all reporting groups
Age, Continuous	34 years n=5 Participants	40 years n=7 Participants	35.5 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized White Non-Hispanic	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Black Non-Hispanic	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian Non-Hispanic	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Low Intensity Anticoagulation n=12 Participants 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. Low intensity anticoagulation: 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 Anticoagulation n=14 Participants 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. Moderate Intensity Anticoagulation: 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.
Number of Participants With Major Bleeding Events	1 Participants	4 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Low Intensity Anticoagulation n=14 Participants 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. Low intensity anticoagulation: 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 Anticoagulation n=12 Participants 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. Moderate Intensity Anticoagulation: 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.
Number of Participants With Thromboembolic Events	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Low Intensity Anticoagulation n=14 Participants 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. Low intensity anticoagulation: 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 Anticoagulation n=12 Participants 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. Moderate Intensity Anticoagulation: 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.
Number of Participants With Cannula-associated Deep Vein Thrombosis	7 Participants	5 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Low Intensity Anticoagulation n=14 Participants 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. Low intensity anticoagulation: 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 Anticoagulation n=12 Participants 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. Moderate Intensity Anticoagulation: 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.
Number of Circuit or Circuit Component Exchanges	2 Exchanges	1 Exchanges

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Low Intensity Anticoagulation n=14 Participants 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. Low intensity anticoagulation: 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 Anticoagulation n=12 Participants 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. Moderate Intensity Anticoagulation: 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.
New Heparin Induced Thrombocytopenia Diagnosis	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Low Intensity Anticoagulation n=14 Participants 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. Low intensity anticoagulation: 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 Anticoagulation n=12 Participants 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. Moderate Intensity Anticoagulation: 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.
Lowest Platelet Count	88 cells per mcL Interval 70.0 to 132.0	130 cells per mcL Interval 115.0 to 170.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Low Intensity Anticoagulation n=12 Participants 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. Low intensity anticoagulation: 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 Anticoagulation n=14 Participants 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. Moderate Intensity Anticoagulation: 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.
Highest Total Bilirubin Values	1.2 mg/dL Interval 0.6 to 1.4	0.9 mg/dL Interval 0.7 to 2.1

SECONDARY outcome

Timeframe: 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