CPB Management & Anticoagulation for Obese Patients

Overseen by Pierre Voisine, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Laval University

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Autoimmune disease, Stroke, Renal failure, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Standard Heparin management, based on total body weight, is not well established for obese patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study is to assess the safety and efficacy of using lean body mass (LBM) to determine pump flow rate and/or Heparin dosage in obese patients undergoing CPB.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients who have taken certain blood thinners like clopidogrel, ticagrelor, or prasugrel within a specific timeframe before surgery. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Heparin for obese patients?

Research shows that unfractionated heparin (UFH) can be effective in obese patients when dosed appropriately, as obesity increases the risk of blood clots. Studies have evaluated UFH dosing in both adults and children, indicating that weight-based dosing can help achieve the desired anticoagulation effect in obese individuals. ^{1 2 3 4 5}

Is unfractionated heparin (UFH) safe for use in obese patients?

Some studies suggest that standard unfractionated heparin (UFH) protocols may lead to over-anticoagulation in obese patients, which could increase the risk of bleeding. However, the safety of UFH in obese patients is still being evaluated, and more research is needed to determine the best dosing strategies to ensure safety. ^{2 4 5 6 7}

How does the treatment for CPB management and anticoagulation differ for obese patients?

This treatment is unique because it focuses on adjusting the heparin dosage based on the specific needs of obese patients, rather than using a standard weight-based approach, which may not be accurate for them. This is important because traditional dosing methods can lead to incorrect anticoagulation levels in obese individuals. ^{2 3 4 8 9}

Research Team

Pierre Voisine, MD

Principal Investigator

University Laval

Eligibility Criteria

This trial is for obese patients (BMI ≥ 30kg/m2) who are at least 18 years old and scheduled for cardiac surgery with cardiopulmonary bypass. It's not suitable for those with allergies to anticoagulants like Heparin, severe kidney or liver issues, certain blood disorders, recent heart attacks or strokes, or women who are pregnant/breastfeeding.

Inclusion Criteria

My BMI is 30 or higher.

I am 18 years old or older.

I am scheduled for heart surgery.

Exclusion Criteria

Known intolerance to protamine

I will be using desmopressin around the time of my surgery.

Permanent pacemaker

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo cardiac surgery with cardiopulmonary bypass, with Heparin dosage and pump flow rate adjusted based on body weight or lean body mass

Peroperative

1 visit (in-person)

Immediate Post-operative Monitoring

Participants are monitored for bleeding and other complications immediately after surgery

24 hours

Follow-up

Participants are monitored for safety and effectiveness, including transfusion requirements and post-operative complications

7 days or until discharge

Treatment Details

Interventions

• Heparin (Anticoagulant)

Trial Overview The study tests if calculating the flow rate of the cardiopulmonary bypass pump and Heparin dosage based on lean body mass instead of total weight is safe and effective in obese patients undergoing heart surgery.

Participant Groups

Group I: Intervention group C Experimental Treatment 2 Interventions

Heparin dose and cardiopulmonary bypass pump flow rate are adjusted for lean body weight. An initial 400 IU/Kg Heparin dose will be administered, with an additional dose of 75 IU/kg if the activated clotting time remains below the 425 seconds target value. The cardiopulmonary bypass pump flow rate of 2.4 L/min/m2 of body surface area will be calculated.

Group II: Intervention group B Experimental Treatment 2 Interventions

Heparin dose is calculated using total body weight and cardiopulmonary bypass pump flow rate is adjusted for lean body weight. An initial 400 IU/Kg Heparin dose will be administered, with an additional dose of 75 IU/kg if the activated clotting time remains below the 425 seconds target value. The cardiopulmonary bypass pump flow rate of 2.4 L/min/m2 of body surface area will be calculated.

Group III: Intervention group A Experimental Treatment 2 Interventions

Heparin dose is adjusted for lean body weight and cardiopulmonary bypass pump flow rate is calculated using total body weight. An initial 400 IU/Kg Heparin dose will be administered, with an additional dose of 75 IU/kg if the activated clotting time remains below the 425 seconds target value. The cardiopulmonary bypass pump flow rate of 2.4 L/min/m2 of body surface area will be calculated.

Group IV: Control group Active Control 2 Interventions

Heparin dose and cardiopulmonary bypass pump flow rate are calculated using total body weight. An initial 400 IU/Kg Heparin dose will be administered, with an additional dose of 75 IU/kg if the activated clotting time remains below the 425 seconds target value. The cardiopulmonary bypass pump flow rate of 2.4 L/min/m2 of body surface area will be calculated.

Who Is Running the Clinical Trial?

Laval University

Lead Sponsor

Trials

439

Recruited

178,000+

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Collaborator

Trials

37

Recruited

9,700+

Findings from Research

In a study of 62 critically ill patients, including non-obese, obese, and morbidly obese individuals, dosing unfractionated heparin (UFH) based on actual body weight resulted in similar effectiveness in achieving therapeutic activated partial thromboplastin times (aPTT) across all groups.

Despite a higher steady-state dose of UFH in non-obese patients, both obese and morbidly obese patients reached therapeutic aPTT levels without major bleeding complications, suggesting that adjusted dosing strategies can be safe and effective for these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of heparin dosing based on actual body weight in non-obese, obese and morbidly obese critically ill patients. Gerlach, AT., Folino, J., Morris, BN., et al.[2021]

In a study of 50 pediatric patients, those with obesity did not show a higher frequency of supratherapeutic anticoagulation when receiving weight-based doses of unfractionated heparin (UFH) compared to nonobese patients, indicating that dosing by actual body weight is safe for both groups.

Obese children required lower starting and maintenance doses of UFH to achieve stable therapeutic anticoagulation levels, suggesting that weight-based dosing may need to be adjusted for this population to avoid overmedication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of weight-based dosing of unfractionated heparin in obese children. Taylor, BN., Bork, SJ., Kim, S., et al.[2013]

In a study of 240 obese patients receiving unfractionated heparin, it was found that total body weight is the best predictor for determining heparin dosage, with patients weighing 150 kg or more requiring an average of 11.3 units/kg per hour to achieve therapeutic levels.

Despite differences in heparin dosage based on weight, the incidence of bleeding complications was similar across all weight groups, suggesting that the dosing protocols used were safe for obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the use of institutional unfractionated heparin protocols for therapeutic anticoagulation in obese patients: a retrospective chart review. Shin, S., Harthan, EF.[2015]

In a study of 326 obese patients (BMI ≥30 kg/m2), high-dose unfractionated heparin (7500 units every 8 hours) was associated with a significantly higher incidence of bleeding events (43%) compared to standard-dose heparin (5000 units every 8 hours) which had a bleeding rate of 29%.

Despite the increased bleeding risk with high-dose UFH, there was no significant difference in the rates of venous thromboembolism between the two dosing regimens, raising concerns about the safety of high-dose UFH for thromboprophylaxis in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of High-Dose Unfractionated Heparin for Prophylaxis of Venous Thromboembolism in Hospitalized Obese Patients. Regis, T., Goriacko, P., Ferguson, N.[2021]

In a study of 78 pediatric patients undergoing cardiac catheterization, including 39 obese patients, there was no significant difference in the response to unfractionated heparin (UFH) between obese and nonobese children, as measured by activated clotting time (ACT).

The study found that the dosing of UFH per kilogram was similar for both groups, suggesting that weight-based dosing of UFH may not need to be adjusted for obese pediatric patients in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heparin dosing in obese pediatric patients in the cardiac catheterization laboratory. Moffett, BS., Teruya, J., Petit, C.[2015]

In a study of obese critically ill patients receiving unfractionated heparin (UFH), those weighing 130 kg or more required lower weight-based infusion rates (13 U/kg/h) compared to those weighing 95 to 104 kg (15.8 U/kg/h), indicating a need for adjusted dosing in heavier patients.

The findings suggest that initiating heparin at appropriate weight-based doses for obese patients can optimize anticoagulation, particularly for those over 165 kg, who have distinct dosing requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unfractionated heparin dosing for therapeutic anticoagulation in critically ill obese adults. Hohner, EM., Kruer, RM., Gilmore, VT., et al.[2018]

Obese patients required significantly lower weight-based infusion rates of unfractionated heparin (UFH) to achieve therapeutic anticoagulation levels compared to non-obese patients, indicating a need for adjusted dosing protocols for this population.

Despite the differences in dosing, there were no significant differences in major bleeding or in-hospital mortality between obese and non-obese patients, suggesting that the modified dosing does not compromise safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of safety and effectiveness of standardized antifactor Xa-based unfractionated heparin protocols in obese versus non-obese patients. Isherwood, M., Murphy, ML., Bingham, AL., et al.[2019]

In a study involving 100 patients (50 obese and 50 nonobese) undergoing cardiac surgery, it was found that using total body weight (TBW) for heparin dosing led to significantly higher plasma heparin concentrations in obese patients, which could pose safety risks.

The research suggests that an initial heparin bolus based on ideal body weight (340 IU/kg) may be more effective in achieving appropriate anticoagulation levels in obese patients, potentially reducing the risk of excessive heparin exposure during cardiopulmonary bypass.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying optimal heparin management during cardiopulmonary bypass in obese patients: A prospective observational comparative study. Haas, E., Fischer, F., Levy, F., et al.[2018]

Seven alternative anticoagulants have been used during cardiopulmonary bypass (CPB) for patients with heparin-induced thrombocytopenia, but they lack standardized dosing and reliable monitoring methods.

Despite the exploration of these alternatives, unfractionated heparin remains the preferred anticoagulant for CPB due to its established safety and efficacy, as well as the absence of proven antidotes for the alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiopulmonary bypass in humans: bypassing unfractionated heparin. Frederiksen, JW.[2019]

References

1. India pubmed.ncbi.nlm.nih.gov

Comparison of heparin dosing based on actual body weight in non-obese, obese and morbidly obese critically ill patients. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Evaluation of weight-based dosing of unfractionated heparin in obese children. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the use of institutional unfractionated heparin protocols for therapeutic anticoagulation in obese patients: a retrospective chart review. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Safety of High-Dose Unfractionated Heparin for Prophylaxis of Venous Thromboembolism in Hospitalized Obese Patients. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Heparin dosing in obese pediatric patients in the cardiac catheterization laboratory. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Unfractionated heparin dosing for therapeutic anticoagulation in critically ill obese adults. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of safety and effectiveness of standardized antifactor Xa-based unfractionated heparin protocols in obese versus non-obese patients. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Identifying optimal heparin management during cardiopulmonary bypass in obese patients: A prospective observational comparative study. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiopulmonary bypass in humans: bypassing unfractionated heparin. [2019]