Heparin Dosing for Percutaneous Coronary Intervention

(HD-PCI Trial)

Overseen By Jessica Tyrwhitt

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Population Health Research Institute

Disqualifiers: Age <18, Chronic occlusion PCI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

16000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different doses of heparin, a blood thinner, affect individuals undergoing a planned heart procedure called percutaneous coronary intervention (PCI). The researchers aim to determine whether a higher or lower dose of heparin enhances the safety or effectiveness of the procedure. Participants will be divided into two groups: one receiving a higher dose and the other a lower dose during their procedure. This trial may suit those scheduled for an elective PCI who can follow up locally. As an unphased trial, it offers participants the chance to contribute to valuable research that could improve future PCI procedures.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that higher doses of unfractionated heparin (UFH) during procedures like heart surgeries are generally safe when administered correctly. Guidelines provide specific targets to ensure safety. Studies have found that even higher doses of UFH are safe when used early in treatment.

For lower doses of UFH, research indicates they are as safe and effective as other blood thinners like bivalirudin. Low-dose UFH has been used successfully in many situations and is well-tolerated.

Both high and low doses of UFH have been widely used, with safety data supporting their use in medical procedures like heart surgeries. This extensive use provides confidence in their safety for patients considering joining clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the optimal dosing of unfractionated heparin (UFH) for percutaneous coronary intervention (PCI), a procedure used to treat narrowed coronary arteries. While the current standard of care involves variable dosing strategies, this trial compares a higher dose of 100 U/kg UFH with a lower dose of 70 U/kg UFH to determine which is more effective and safer for patients undergoing PCI. By standardizing the dosing and comparing the outcomes, researchers aim to improve the safety and efficacy of PCI procedures, potentially leading to better patient outcomes and reduced risk of complications like bleeding or clotting.

What evidence suggests that this trial's treatments could be effective for PCI?

Research has shown that using unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) can help prevent blood clots. Most doctors recommend a dose of 70-100 units per kilogram (U/kg) for this procedure. In this trial, participants will receive either a higher dose of UFH, specifically 100 U/kg, or a lower dose, specifically 70 U/kg, during PCI. While strong evidence does not support routinely using higher doses at the start of PCI, they are generally considered safe. Conversely, lower doses of UFH have also achieved high success rates with few complications. Overall, both higher and lower doses of UFH are commonly used and have been linked to positive outcomes in PCI. ^{1 4 6 7 8}

Who Is on the Research Team?

Sanjit Jolly, MD

Principal Investigator

Population Health Research Institute

Are You a Good Fit for This Trial?

This trial is for adults who need an elective procedure to open blocked arteries in the heart (PCI). Hospitals must submit data to a registry and follow the heparin dose policy. It's not for those under 18, planning a specific complex PCI, or non-residents who can't be followed up locally.

Inclusion Criteria

I am scheduled for a planned procedure to open blocked arteries in my heart.

Hospitals will be eligible to participate if they meet the following criteria:

I am scheduled for a planned procedure to open blocked arteries in my heart.

Exclusion Criteria

I am scheduled for a procedure to open a completely blocked heart artery.

Non-resident precluding follow up through local registries

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a higher dose (100 U/kg) or lower dose (70 U/kg) of unfractionated heparin during elective PCI procedures

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on outcomes like death, myocardial infarction, or target vessel revascularization

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Higher Dose UFH
• Lower Dose UFH

Trial Overview The HD PCI trial compares two dosing strategies of heparin: a higher dose versus a lower dose during heart artery-opening procedures. Patients are randomly assigned to either group across different hospitals that switch policies periodically.

How Is the Trial Designed?

Group I: Higher Dose Unfractionated Heparin Treatment Period Active Control 1 Intervention

A centre wide policy of administering 100 U/kg bolus of intravenous unfractionated heparin (UFH) for elective percutaneous coronary intervention (PCI) procedures will be implemented during the Higher Dose UFH treatment period.

Group II: Lower Dose Unfractionated Heparin Treatment Period Active Control 1 Intervention

A centre wide policy of administering 70 U/kg bolus of intravenous UFH for elective PCI procedures will be implemented during the Lower Dose UFH treatment period.

Higher Dose UFH is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Unfractionated Heparin for:

• Prevention of thromboembolic disorders
• Treatment of deep vein thrombosis
• Treatment of pulmonary embolism
• Prevention of clotting in extracorporeal circuits during cardiopulmonary bypass surgery

Approved in United States as Unfractionated Heparin for:

• Prevention and treatment of deep vein thrombosis and pulmonary embolism
• Prevention of postoperative deep vein thrombosis and pulmonary embolism in patients undergoing major abdominothoracic surgery
• Prevention of clotting in arterial and cardiac surgery

Approved in Canada as Unfractionated Heparin for:

• Thromboembolic disorders
• Deep vein thrombosis
• Pulmonary embolism
• Cardiopulmonary bypass surgery

Approved in China as Unfractionated Heparin for:

• Prevention and treatment of thromboembolic disorders
• Deep vein thrombosis
• Pulmonary embolism
• Cardiopulmonary bypass surgery

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Published Research Related to This Trial

In a study of 123 STEMI patients treated with tenecteplase and intravenous UFH, low-dose Enoxaparin (4,000 U once daily) showed comparable safety and efficacy to full-dose Enoxaparin (100 U/kg twice daily) in preventing complications like hemorrhages and reinfarction.

Both dosing regimens resulted in similar rates of venous thromboembolism and infarct-related artery patency, suggesting that the lower dose may be a preferable option due to its ease of use without compromising patient safety or outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous enoxaparin following thrombolysis and intravenous unfractionated heparin in ST-elevation acute myocardial infarction: safety and efficacy of low vs full dose. Rubboli, A., Gatti, C., Spinolo, L., et al.[2018]

In a study of 41,631 patients with STEMI, pretreatment with unfractionated heparin (UFH) before PCI significantly reduced coronary artery occlusion, with a number needed to treat (NNT) of 12, indicating it is effective in improving coronary outcomes.

UFH pretreatment also showed a potential reduction in 30-day mortality (NNT of 94), but this finding was not consistent across all analyses, suggesting further investigation is needed to confirm its impact on mortality without increasing the risk of major bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretreatment with heparin in patients with ST-segment elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Emilsson, OL., Bergman, S., Mohammad, MA., et al.[2023]

In a study of 200 patients undergoing elective percutaneous coronary intervention (PCI), low-dose intracoronary unfractionated heparin (UFH) was found to be as safe and effective as standard intravenous UFH, with similar rates of major complications like death and myocardial infarction at both 30 days and 6 months.

The use of low-dose intracoronary UFH resulted in lower healthcare costs at 30 days compared to the control group, suggesting a more economical approach to anticoagulation during PCI without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The REDUCED (a RandomisED stUdy Comparing standard systemic anticoagulation thErapy to low Dose intracoronary anticoagulation therapy for elective percutaneous coronary intervention) trial. A novel pharmacologic regime for elective percutaneous coronary intervention. Ari, H., Kivaç, E., Ari, S., et al.[2019]

In a study of 580 patients undergoing percutaneous coronary intervention (PCI) for STEMI, enoxaparin was found to be more effective than unfractionated heparin (UFH) in reducing the risk of death and recurrent myocardial infarction, both during hospitalization and up to 30 days post-procedure.

Patients receiving enoxaparin were more likely to achieve therapeutic anticoagulation during the procedure without an increase in major bleeding events, suggesting it is a safer and more effective option for anticoagulation in STEMI patients undergoing PCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention. Brieger, D., Collet, JP., Silvain, J., et al.[2022]

In a study of 66 hemodialysis patients, switching from a standard-dose to a low-dose unfractionated heparin (UFH) protocol significantly reduced the average UFH dose while maintaining dialysis adequacy, indicating that lower doses can be effective and safe.

The low-dose UFH protocol allowed for a reduction in the weekly dose of erythropoiesis-stimulating agents (ESA) without negatively impacting hemoglobin levels, suggesting potential benefits in anemia management for patients undergoing hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose heparin in hemodialysis. Murea, M., Russell, GB., Daeihagh, P., et al.[2022]

This study will evaluate the safety of two different doses of unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) in about 4,000 high-risk patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who were initially treated with fondaparinux.

The primary focus is on comparing a standard ACT-guided UFH regimen to a lower weight-adjusted UFH dose, with the goal of determining which regimen results in fewer major bleeding complications and better overall clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fondaparinux with UnfracTionated heparin dUring Revascularization in Acute coronary syndromes (FUTURA/OASIS 8): a randomized trial of intravenous unfractionated heparin during percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. Steg, PG., Mehta, S., Jolly, S., et al.[2018]

In a study of 698 patients undergoing elective percutaneous coronary intervention (PCI), a fixed dose of 3000 U of unfractionated heparin (UFH) showed similar effectiveness in preventing troponin I release compared to a weight-adjusted dose of 70 U/kg, indicating that lower dosing may be sufficient.

Both dosing strategies resulted in no major complications, such as deaths or significant bleeding, suggesting that a fixed dose of heparin is safe for use during PCI in patients with stable angina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unfractionated heparin during elective PCI: fixed dose or weight adjusted? Kidambi, A., Mayurathan, G., Viswanathan, G., et al.[2015]

This study evaluated the safety of low-dose unfractionated heparin (2000 to 3000 units) during intravascular ultrasound (IVUS) studies in 108 cardiac transplant patients, finding no thromboembolic events and only one minor complication (catheter-induced coronary dissection).

The results suggest that low-dose heparin can be safely administered shortly after endomyocardial biopsy during IVUS procedures, indicating its potential for use in similar clinical settings without significant adverse outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose unfractionated heparin administration during intravascular ultrasound studies is safe even shortly after endomyocardial biopsy in cardiac transplant patients. Arsanjani, R., Khitri, A., Hashemzadeh, M., et al.[2019]

A study comparing two heparin dosing protocols found that both fully weight-based and non-weight-based titration methods were similarly effective in achieving therapeutic activated partial thromboplastin time (aPTT), with a high success rate of around 96% in both groups.

However, patients on the non-weight-based protocol had a lower initial success rate in achieving therapeutic aPTT when treated under low-target protocols, indicating that while both methods are effective overall, the fully weight-based approach may be more reliable for certain patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a Fully Weight-Based Protocol with a Non-Weight-Based Dosage Titration Protocol for IV Unfractionated Heparin: A Before-and-After Study. Cameron, T., Chua, D., Shalansky, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1767377/

Heparin dose during percutaneous coronary intervention There are no data to support routine administration of high doses of heparin at the initiation of every PCI procedure. The dose of heparin must be tailored to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04049591

NCT04049591 | Higher vs. Lower Dose Heparin for PCI The primary objective of HD PCI is to compare the effect of a policy of higher dose heparin (100 U/kg) use to a policy of lower dose heparin (70 U/kg) use on ...

3. academic.oup.com academic.oup.com/eurheartj/article/46/39/3888/8220871

Heparin administration at first medical contact vs immediately ... Early administration of unfractionated heparin (UFH), commonly used in many national STEMI networks, appears to be both safe and associated with ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1443950623043627

Variability in Contemporary Heparin Prescription and ... Of 430 ICs surveyed, 148 responded (response rate, 34.4%). Most ICs (84.4%) prescribed 70–100 IU/kg of UFH for PCI. Over half of ICs (58.7%) routinely measured ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10883739/

Percutaneous Coronary Intervention with Procedural ... In this study, PCI performed with UFH was related to low rate of thrombotic and bleeding complications when no ACT guidance was used. To our ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1936879809004737

Comparison of Safety and Efficacy of Bivalirudin Versus ... The aim of this study was to determine the efficacy and safety of bivalirudin versus low-dose unfractionated heparin (UFH) in percutaneous peripheral ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04049591

NCT04049591 | Higher vs. Lower Dose Heparin for PCI A centre wide policy of administering 100 U/kg bolus of intravenous unfractionated heparin (UFH) for elective percutaneous coronary intervention (PCI) ...

8. jacc.org jacc.org/doi/full/10.1016/S0735-1097(23)03665-3

HEPARIN FAILURE DURING PERCUTANEOUS ... This case demonstrates a concern for an ineffective lot of UFH administered in the cardiac catheterization lab and a multidisciplinary team ...