Coronary Artery Disease (CAD)
Conditions
Keywords
Percutaneous Coronary Intervention (PCI)
Brief summary
The primary objective is to evaluate the safety and feasibility of using M118 as an anticoagulant in the target population of subjects with stable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). The secondary objectives are to evaluate the effect of M118 on procedural indices including procedure success, abrupt closure, post-procedure TIMI flow, and catheter thrombus. Substudy Primary Objective The primary objective of the substudy is to characterize the pharmacokinetic and pharmacodynamic profile of M118 among subjects with stable coronary artery disease undergoing elective PCI.
Interventions
DRUGM118
intravenous (IV) infusion
DRUGUnfractionated Heparin
IV infusion
Sponsors
Momenta Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 19 years * Ability to give informed consent * Documented stable CAD with a significant lesion in a native coronary artery amenable to PCI with one stent * Planned single vessel intervention
Exclusion criteria
* Myocardial infarction or unstable angina within the prior 7 days * Target lesion is a chronic total occlusion (present for longer than 3 months) * Target lesion with angiographically visible thrombus or in-stent thrombosis * Target lesion is in a bypass graft * Planned use of a GP IIb/IIIa inhibitor or planned use of atherectomy including directional, rotational, or laser * Known allergies or sensitivities to heparin, pork, or pork-containing products * History of HIT * Hemodynamic instability * Stroke or Transient Ischemic Attack (TIA) in the prior 3 months * Active bleeding or bleeding diathesis * Trauma or major surgery in the preceding month or planned surgery or PCI within the 30 days after the index PCI * Suspected aortic dissection * Receiving oral anticoagulation therapy * Receipt of LMWH or of UFH (except for that used during the diagnostic portion of the index procedure) within the prior 7 days * ACT \> 200 prior to study drug administration * Severe, untreated hypertension at the time of the index PCI procedure (systolic blood pressure of \> 180 mm Hg, diastolic blood pressure \> 90 mm Hg) * Hemoglobin level of less than 10.0 g/dl or a hematocrit below 30% * Platelet count of less than 100,000 per cubic millimeter or more than 600,000 per cubic millimeter * Creatinine clearance \< 30 mL/min * Any malignancy within the prior 5 years with the exception of non-melanoma skin cancers * Prior enrollment in EMINENCE trial or currently receiving other experimental therapy * Pregnant or lactating if subject is female Substudy: Inclusion: * Ability to give informed consent * Participation in the main study protocol Exclusion: -Inability to provide the blood specimens required by the substudy protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical Events Defined as the Composite of 30-day Death, MI, Repeat Revascularization, Catheter Thrombus, Stroke, Thrombocytopenia, Bailout Use of Glycoprotein IIb/IIIa Inhibitors and Bleeding. | 30 days |
Countries
Canada, United States
Participant flow
Recruitment details
503 patients undergoing elective percutaneous coronary intervention at 43 centers in the United States and Canada were randomized
Participants by arm
| Arm | Count |
|---|---|
| 70 U/kg of Unfractionated Heparin Given IV Venous injection (IV) of 70 units per kilogram (U/kg) of unfractionated heparin prior to percutaneous coronary intervention. If procedure lasts longer than 30 minutes a 1/2 rebolus of the original therapy will be given. | 151 |
| 50 IU/KG of M118 Venous injection of 50 international units per kilogram (IU/kg) of M118 prior to percutaneous coronary intervention. If procedure lasts longer than 30 minutes a 1/2 rebolus of the original therapy will be given. | 44 |
| 75 IU/KG of M118 Venous injection of 75 IU/kg of M118 prior to percutaneous coronary intervention. If procedure lasts longer than 30 minutes a 1/2 rebolus of the original therapy will be given. | 152 |
| 100 IU/KG of M118 Venous injection of 100 IU/kg of M118 prior to percutaneous coronary intervention. If procedure lasts longer than 30 minutes a 1/2 rebolus of the original therapy will be given. | 156 |
| Total | 503 |
Baseline characteristics
| Characteristic | 70 U/kg of Unfractionated Heparin Given IV | 50 IU/KG of M118 | 75 IU/KG of M118 | 100 IU/KG of M118 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.8 years | 62.9 years | 65.3 years | 63.0 years | 63.9 years |
| Sex: Female, Male Female | 35 Participants | 13 Participants | 44 Participants | 47 Participants | 139 Participants |
| Sex: Female, Male Male | 116 Participants | 31 Participants | 108 Participants | 109 Participants | 364 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 116 / 151 | 36 / 44 | 116 / 152 | 114 / 156 |
| serious Total, serious adverse events | 20 / 151 | 5 / 44 | 15 / 152 | 15 / 156 |
Outcome results
Primary
Clinical Events Defined as the Composite of 30-day Death, MI, Repeat Revascularization, Catheter Thrombus, Stroke, Thrombocytopenia, Bailout Use of Glycoprotein IIb/IIIa Inhibitors and Bleeding.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 70 U/kg of Unfractionated Heparin Given IV | Clinical Events Defined as the Composite of 30-day Death, MI, Repeat Revascularization, Catheter Thrombus, Stroke, Thrombocytopenia, Bailout Use of Glycoprotein IIb/IIIa Inhibitors and Bleeding. | 47 patients experiencing an event |
| 50 IU/kg of M118 | Clinical Events Defined as the Composite of 30-day Death, MI, Repeat Revascularization, Catheter Thrombus, Stroke, Thrombocytopenia, Bailout Use of Glycoprotein IIb/IIIa Inhibitors and Bleeding. | 10 patients experiencing an event |
| 75 IU/KG of M118 | Clinical Events Defined as the Composite of 30-day Death, MI, Repeat Revascularization, Catheter Thrombus, Stroke, Thrombocytopenia, Bailout Use of Glycoprotein IIb/IIIa Inhibitors and Bleeding. | 43 patients experiencing an event |
| 100 IU/kg of M118 | Clinical Events Defined as the Composite of 30-day Death, MI, Repeat Revascularization, Catheter Thrombus, Stroke, Thrombocytopenia, Bailout Use of Glycoprotein IIb/IIIa Inhibitors and Bleeding. | 47 patients experiencing an event |