Optimizing the Anticoagulation Regimen of Enoxaparin During Percutaneous Coronary Intervention (OPTIENOX-PCI) (OPTIENOX-PCI)

Optimizing the Anticoagulation Regimen of Enoxaparin During Percutaneous Coronary Intervention

The OPTIENOX-PCI is a single-center, prospective, randomized, open-label, controlled study, which is designed to assess the anticoagulation profile of: 1) High-dose (0.75 mg/kg) vs. Standard-dose (0.5 mg/kg) enoxaparin; 2) Staged-dose (0.5+0.25 mg/kg) vs. Single-dose (0.75 mg/kg) enoxaparin in about 376 patients who plan to undergo elective trans-radial coronary angiography (CAG) with or without subsequent percutaneous coronary intervention (PCI).

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Percutaneous Coronary Intervention
• Intervention / Treatment: Drug: Enoxaparin (Staged-dose PCI Group); Drug: Enoxaparin (Single-dose PCI Group); Drug: Enoxaparin (High-dose Group); Drug: Enoxaparin (Standard-dose Group)

Detailed Description

Once the radial sheaths are successfully inserted, eligible patients will be consecutively, sequentially, and randomly assigned in a 1:1 ratio and with a block size of 4 to either the Planned Single-dose group (0.75 mg/kg) or the Planned Staged-dose group (0.5 ± 0.25 mg/kg).

The first dose enoxaparin will be administered immediately after randomization. In the Planned Single-dose group, enoxaparin 0.75 mg/kg will be given to all patients before CAG irrespective of whether they will undergo subsequent PCI or not. In the Planned Staged-dose group, enoxaparin 0.5 mg/kg will be administered to all patients before CAG and additional 0.25 mg/kg will be given only to those who will undergo subsequent PCI immediately before PCI.

Trans-radial CAG will be performed immediately after the first dose enoxaparin is given. When the angiographic results are available, whether the patients will proceed to subsequent PCI or not will be at the discretion of the procedure operators, who are blinded to the assignment of enoxaparin dosing regimens. Patients who undergo CAG alone in each group will be defined as the High-dose (0.75 mg/kg) and the Standard-dose (0.5 mg/kg) groups, respectively; while, patients who undergo both CAG and subsequent PCI in each group will be defined as the Single-dose PCI (0.75 mg/kg) and the Staged-dose PCI (0.5 + 0.25 mg/kg) groups, respectively.

Anti-Xa levels will be assessed: 1) at 0 min (immediately before), 10 min and 90 min after the first dose enoxaparin is given (CAG-0 min, CAG-10 min, and CAG-90 min, respectively) in all patients; 2) at 0 min (immediately before) and 10 min after the beginning of PCI (PCI-0 min and PCI-10 min, respectively), and at the end of PCI (PCI-End) in patients undergoing PCI.

Target anticoagulation is defined as: 1) anti-Xa level of 0.5-1.8 IU/ml in patients in the High-dose and Standard-dose groups; 2) anti-Xa level of 0.5-1.2 IU/ml before PCI and anti-Xa level of 0.5-1.8 IU/ml from the beginning of PCI up to 90 min after the first dose enoxaparin is given in the Single-dose PCI and the Staged-dose PCI groups.

The information on cardiac ischemic and bleeding events will be collected 24 h after randomization.

The OPTIENOX-PCI study will assess the anticoagulation profile between: 1) the High-dose and the Standard-dose groups (0.75 mg/kg vs. 0.5 mg/kg); 2) the Staged-dose PCI and the Single-dose PCI groups (0.5+0.25 mg/kg vs. 0.75 mg/kg). The result of the present study will provide pharmacodynamical data for the design of future outcome studies.

• Study Type: Interventional
• Enrollment (Actual): 378
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of written informed consent.
2. Aged 18 years or older, male or female.
3. Documented stable coronary artery disease (SCAD) or non-ST-segment elevation acute coronary syndromes (NSTE-ACS).
4. Plan to undergo elective trans-radial coronary angiography with or without subsequent PCI.
5. No fibrinolytic, or anticoagulant, or parenteral antiplatelet therapy within 7 days of screening.
6. Negative cardiac troponin test within 7 days of screening.
7. Trans-radial approach successfully established.
8. Females who are either post-menopausal > 1 year or surgically sterile.

Exclusion Criteria:

1. Recent (within 30 days of screening) acute myocardial infarction, including ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction.
2. The aim of the index coronary angiography is to undergo primary PCI or early PCI for acute coronary syndromes.
3. Any indications other than coronary artery disease (e.g., atrial fibrillation, prosthetic heart valve, venous thromboembolism, ventricular thrombosis, et al) for fibrinolytic or anticoagulant treatment during study period.
4. Planned use of any fibrinolytic or antithrombotic agents, with the exception of enoxaparin, aspirin, clopidogrel, and ticagrelor during study period.
5. Planned coronary artery bypass graft (CABG) during study period.

6. Increased bleeding risk, including

   • any history of intracranial, intraocular, retroperitoneal, or spinal bleeding;
   • recent (within 30 days of screening) gastrointestinal (GI) bleeding;
   • recent (within 30 days of screening) major trauma or major surgery;
   • planned surgery or other invasive procedure during study period;
   • sustained uncontrolled hypertension (systolic blood pressure [SBP] > 180 mmHg or diastolic blood pressure [DBP] > 100 mmHg) within 7 days of screening;
   • history of hemorrhagic disorders, e.g., haemophilia, von Willebrand's disease;
   • inability to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during study period;
   • platelet count less than 100,000/mm3 or hemoglobin < 10 g/dL within 7 days of screening.
7. Contraindications for enoxaparin, e.g., hypersensitivity, active bleeding, bleeding diathesis, coagulation disorders, acute infectious endocarditis, thrombocytopenia (including heparin-induced thrombocytopenia), cerebral hemorrhage, severe liver of kidney diseases, severe hypertension, stroke, retinopathy, et al.
8. History of intolerance to enoxaparin.
9. Patient requires dialysis or has a creatinine clearance < 30 mL/min as calculated by the Cockcroft-Gault equation: Clcr = (140 - Age) × WT / (72 × Scr) (× 0.85 for females), where WT is weight in kg, Scr is serum creatinine in mg/dL measured within 7 days of screening.
10. Any acute or chronic unstable conditions in the past 30 days which, in the opinion of the investigator, may either put the patient at risk or influence the result of the study, e.g., active cancer, et al.
11. Any condition that may increase the risk of non-compliance to study protocol or follow-up, e.g., history of drug addiction or alcohol abuse, et al.
12. Patients who has previously been randomized in this study.
13. Participation in another investigational drug or device study within 30 days of screening.
14. Involvement in the planning and conduct of the study (applies to investigators, contract research organization staff, and study site staff).
15. Known pregnancy, breast-feeding, or intend to become pregnant during the study period.
16. Any condition which in the opinion of the investigator would make it unsafe or unsuitable for the patient to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enoxaparin (Staged-dose PCI Group); Enoxaparin 0.5 mg/kg at the beginning of coronary angiography (i.e., insertion of angiographic catheter) and additional enoxaparin 0.25 mg/kg at the beginning of PCI (i.e., insertion of guiding catheter).	Drug: Enoxaparin (Staged-dose PCI Group); Enoxaparin 0.5+0.25 mg/kg administered intravenously.; Other Names: Clexane
Active Comparator: Enoxaparin (Single-dose PCI Group); Enoxaparin 0.75 mg/kg at the beginning of coronary angiography (i.e., insertion of angiographic catheter) and NO additional enoxaparin at the beginning of PCI (i.e., insertion of guiding catheter).	Drug: Enoxaparin (Single-dose PCI Group); Enoxaparin 0.75 mg/kg administered intravenously.; Other Names: Clexane
Experimental: Enoxaparin (High-dose Group); Enoxaparin 0.75 mg/kg at the beginning of coronary angiography (i.e., insertion of angiographic catheter).	Drug: Enoxaparin (High-dose Group); Enoxaparin 0.75 mg/kg administered intravenously.; Other Names: Clexane
Active Comparator: Enoxaparin (Standard-dose Group); Enoxaparin 0.5 mg/kg at the beginning of coronary angiography (i.e., insertion of angiographic catheter).	Drug: Enoxaparin (Standard-dose Group); Enoxaparin 0.5 mg/kg administered intravenously.; Other Names: Clexane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Xa level (CAG-90 min) in the High-dose vs. the Standard-dose group.	The anti-Xa level (CAG-90 min) in the High-dose vs. the Standard-dose group.	At 90 min after the first dose enoxaparin is given.
Anti-Xa level (CAG-90 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The anti-Xa level (CAG-90 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 90 min after the first dose enoxaparin is given.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Xa level (CAG-10 min) in the High-dose vs. the Standard-dose group.	The anti-Xa level (CAG-10 min) in the High-dose vs. the Standard-dose group.	At 10 min after the first dose enoxaparin is given.
Anti-Xa level (CAG-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The anti-Xa level (CAG-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 10 min after the first dose enoxaparin is given.
Anti-Xa level (PCI-0 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The anti-Xa level (PCI-0 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 0 min (immediately before) PCI.
Anti-Xa level (PCI-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The anti-Xa level (PCI-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 10 min after the beginning of PCI.
Anti-Xa level (PCI-End) in the Staged-dose PCI vs. the Single-dose PCI group.	The anti-Xa level (PCI-End) in the Staged-dose PCI vs. the Single-dose PCI group.	At the end of PCI.
Target anticoagulation (CAG-90 min) in the High-dose vs. the Standard-dose group.	The rate of target anticoagulation (CAG-90 min) in the High-dose vs. the Standard-dose group.	At 90 min after the first dose enoxaparin is given.
Target anticoagulation (CAG-90 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The rate of target anticoagulation (CAG-90 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 90 min after the first dose enoxaparin is given.
Target anticoagulation (CAG-10 min) in the High-dose vs. the Standard-dose group.	The rate of target anticoagulation (CAG-10 min) in the High-dose vs. the Standard-dose group.	At 10 min after the first dose enoxaparin is given.
Target anticoagulation (CAG-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The rate of target anticoagulation (CAG-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 10 min after the first dose enoxaparin is given.
Target anticoagulation (PCI-0 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The rate of target anticoagulation (PCI-0 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 0 min (immediately before) PCI.
Target anticoagulation (PCI-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	The rate of target anticoagulation (PCI-10 min) in the Staged-dose PCI vs. the Single-dose PCI group.	At 10 min after the beginning of PCI.
Target anticoagulation (PCI-End) in the Staged-dose PCI vs. the Single-dose PCI group.	The rate of target anticoagulation (PCI-End) in the Staged-dose PCI vs. the Single-dose PCI group.	At the end of PCI.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac events (MACE) in the High-dose vs. the Standard-dose group.	The proportion of patients with the composite of death, or myocardial infarction, or urgent coronary revascularization, or definite or probable stent thrombosis in the High-dose vs. the Standard-dose group.	Up to 24 hours.
Major adverse cardiac events (MACE) in the Staged-dose PCI vs. the Single-dose PCI group.	The proportion of patients with the composite of death, or myocardial infarction, or urgent coronary revascularization, or definite or probable stent thrombosis in the Staged-dose PCI vs. the Single-dose PCI group.	Up to 24 hours.
Thrombolysis in myocardial infarction (TIMI) major or minor bleeding in the High-dose vs. the Standard-dose group.	The proportion of patients with the composite of TIMI major or minor bleeding in the High-dose vs. the Standard-dose group.	Up to 24 hours.
Thrombolysis in myocardial infarction (TIMI) major or minor bleeding in the Staged-dose PCI vs. the Single-dose PCI group.	The proportion of patients with the composite of TIMI major or minor bleeding in the Staged-dose PCI vs. the Single-dose PCI group.	Up to 24 hours.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Zhenyu Liu, M.D., Department of Cardiology, Peking Union Medical College Hospital

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2017
• Primary Completion (Actual): April 20, 2022
• Study Completion (Actual): July 14, 2022

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 8, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Anticoagulation; Enoxaparin; Dose
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin; Enoxaparin sodium
• Other Study ID Numbers: PUMCH-2016-2.24; JS-1286 (Other Identifier: Ethics Committee of Peking Union Medical College Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No