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The purpose of this study is to demonstrate that patients receiving cangrelor infusion before coronary artery bypass grafting have an acceptable safety profile and can undergo surgery without excessive bleeding peri-operatively.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cangrelor | Experimental | Cangrelor was administered as a continuous IV infusion of 0.75µg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
|
| Placebo | Placebo Comparator | A placebo infusion was administered as a continuous IV infusion of 0.75µg/kg/min for a minimum of 48 hours and a maximum of 7 days, to maintain the blind. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cangrelor | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Stage I: Percentage of Patient Samples That Maintained Platelet Inhibition Levels of Greater Than or Equal to 60% as Reported by the VerifyNow P2Y12 Point of Care Assay. | Endpoint was selected as an approximation of the antiplatelet effect expected to be maintained if oral P2Y12 inhibitors had not been discontinued (60% inhibition of platelets). | During study drug infusion up to 1-6 hours prior to surgery |
| Stage II: The Percentage of Patients That Maintained Platelet Reaction Units (PRU) < 240, as Determined by the VerifyNow P2Y12 Point of Care Assay, Measured During Study Drug Infusion Pre-surgery. | This endpoint was selected as it is considered by consensus of the Working Group on Platelet Reactivity to be the threshold for the level of platelet inhibition required to maintain a low risk of coronary thrombosis and cardiac ischemic events. Patients had multiple samples and all "on-infusion" samples had to be <240 PRU to meet the endpoint. | During study drug infusion up to 1-6 hours prior to surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Stage II: Analysis of Platelet Reactivity (ITT Population) / Patients With Platelet Reactivity < 240 PRU | This endpoint analyzed the percent of patients with platelet reactivity < 240 PRU at the following timepoints:
| baseline until just prior to surgery (post infusion) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eric Topol, MD | Scripps | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scripps Clinic / Scripps Green Hospital | La Jolla | California | 92037 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22253393 | Derived | Angiolillo DJ, Firstenberg MS, Price MJ, Tummala PE, Hutyra M, Welsby IJ, Voeltz MD, Chandna H, Ramaiah C, Brtko M, Cannon L, Dyke C, Liu T, Montalescot G, Manoukian SV, Prats J, Topol EJ; BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012 Jan 18;307(3):265-74. doi: 10.1001/jama.2011.2002. |
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Stage I was an open-label, dose-finding stage to identify the dose of cangrelor that achieved a level of antiplatelet effect after discontinuation of oral P2Y12 therapy equivalent to the previous oral P2Y12 maintenance therapy. These patients were not enrolled in Stage II.
Stage II was randomized, double-blind, placebo-controlled.
This study enrolled patients with acute coronary syndrome (ACS) or who had previously received stents, who were required to discontinue maintenance oral P2Y12 therapy before cardiac surgery. Patients who had discontinued oral therapy within the previous 72 hours were eligible. Patients were hospitalized during the enrollment period.
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| ID | Title | Description |
|---|---|---|
| FG000 | Stage I, Cohort I - 0.5 mcg/kg/Min Cangrelor | Patients who received cangrelor as a continuous IV infusion of 0.5 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| FG001 | Stage I, Cohort II - 0.75 mcg/kg/Min Cangrelor | Patients who received cangrelor as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| FG002 | Stage II - Cangrelor Arm (0.75 mcg/kg/Min ) | Patients who received cangrelor as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| FG003 | Stage II - Placebo Arm | Patients who received matching placebo as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
This is the Safety Population: Includs both Stage I and Stage II patients who received any study drug and were classified according to the actual treatment received. Stage I (open-label) patients were analyzed based on the dose they received; Stage II (randomized) patients were analyzed based on the actual treatment, cangrelor or placebo, received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Stage I, Cohort I - 0.5 mcg/kg/Min Cangrelor | Patients who received cangrelor as a continuous IV infusion of 0.5 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| BG001 | Stage I, Cohort II - 0.75 mcg/kg/Min Cangrelor |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Stage I: Percentage of Patient Samples That Maintained Platelet Inhibition Levels of Greater Than or Equal to 60% as Reported by the VerifyNow P2Y12 Point of Care Assay. | Endpoint was selected as an approximation of the antiplatelet effect expected to be maintained if oral P2Y12 inhibitors had not been discontinued (60% inhibition of platelets). | Posted | Number | percentage of samples | During study drug infusion up to 1-6 hours prior to surgery | samples | Participants |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stage I, Cohort I - Cangrelor 0.5 mcg/kg/Min | Patients who received cangrelor as a continuous IV infusion of 0.5 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| angina pectoris | Cardiac disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| angina pectoris | Cardiac disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Meredith Todd - Sr. Director Program Management | The Medicines Company | +1.973.290.6088 | meredith.todd@themedco.com |
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| ID | Term |
|---|---|
| D054058 | Acute Coronary Syndrome |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C117446 | cangrelor |
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Placebo IV infusion administered in the same fashion as the active study drug in order to maintain the blind in the study. |
|
| Incidence of Excessive Coronary Artery Bypass Graft (CABG)-Related Bleeding | Defined as the occurrence of surgical re-exploration, 24-hour chest tube output of >1.5 liters (L), and/or packed red blood cell transfusions > 4 units | Randomization through Hospital discharge |
| Non-CABG (Preoperative) Bleeding - Protocol-defined GUSTO Severe/Life-threatening, Moderate and Mild | Randomization until start of CABG surgery |
| Patients With Blood Product Transfusions up to 7 Days After Surgery or Discharge, Whichever Was Sooner | Through 7 days or hospital discharge, whichever was sooner |
Patients who received cangrelor as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days.
| BG002 | Stage II Cangrelor Arm (0.75 mcg/kg/Min) | Patients who received cangrelor as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| BG003 | Stage II Placebo Arm | Patients who received matching placebo as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | This population in Region of Enrollment, represents the total number of subjects enrolled/randomized, and does not exclude any patients. Therefore there are more patients represented here versus in the Safety Population. | Number | participants |
|
Patients who received cangrelor as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days.
|
|
| Primary | Stage II: The Percentage of Patients That Maintained Platelet Reaction Units (PRU) < 240, as Determined by the VerifyNow P2Y12 Point of Care Assay, Measured During Study Drug Infusion Pre-surgery. | This endpoint was selected as it is considered by consensus of the Working Group on Platelet Reactivity to be the threshold for the level of platelet inhibition required to maintain a low risk of coronary thrombosis and cardiac ischemic events. Patients had multiple samples and all "on-infusion" samples had to be <240 PRU to meet the endpoint. | Based on available data from ITT population; ITT population (Cangrelor N = 93) / (Placebo N = 90). Valid PRU results were not available during the infusion period for 15 patients (9 cangrelor and 6 placebo). | Posted | Number | Percent of patients | During study drug infusion up to 1-6 hours prior to surgery |
|
|
|
| Secondary | Stage II: Analysis of Platelet Reactivity (ITT Population) / Patients With Platelet Reactivity < 240 PRU | This endpoint analyzed the percent of patients with platelet reactivity < 240 PRU at the following timepoints:
| Posted | Number | percent of patients | baseline until just prior to surgery (post infusion) |
|
|
|
| Secondary | Incidence of Excessive Coronary Artery Bypass Graft (CABG)-Related Bleeding | Defined as the occurrence of surgical re-exploration, 24-hour chest tube output of >1.5 liters (L), and/or packed red blood cell transfusions > 4 units | This analysis included only those patients who proceeded to have a CABG surgery as required per the protocol. The patients who did not have a CABG surgery were excluded from the denominator. | Posted | Number | Patients | Randomization through Hospital discharge |
|
|
|
| Secondary | Non-CABG (Preoperative) Bleeding - Protocol-defined GUSTO Severe/Life-threatening, Moderate and Mild | This analysis included only those patients who proceeded to have a CABG surgery as required per the protocol. The patients who did not have a CABG surgery were excluded from the denominator. | Posted | Number | participants | Randomization until start of CABG surgery |
|
|
|
| Secondary | Patients With Blood Product Transfusions up to 7 Days After Surgery or Discharge, Whichever Was Sooner | Posted | Number | patients | Through 7 days or hospital discharge, whichever was sooner |
|
|
|
| 0 |
| 5 |
| 3 |
| 5 |
| EG001 | Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min | Patients who received cangrelor as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. | 0 | 6 | 5 | 6 |
| EG002 | Stage II - Cangrelor Arm (0.75 mcg/kg/Min) | Patients who received cangrelor as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. | 11 | 106 | 27 | 106 |
| EG003 | Stage II - Placebo Arm | Patients who received matching placebo as a continuous IV infusion of 0.75 mcg/kg/min for a minimum of 48 hours and a maximum of 7 days. | 9 | 101 | 23 | 101 |
| atrial fibrillation | Cardiac disorders |
|
| cardiac arrest | Cardiac disorders |
|
| cardiac asthma | Cardiac disorders |
|
| cardiac failure | Cardiac disorders |
|
| cardiogenic shock | Cardiac disorders |
|
| cardiopulmonary failure | Cardiac disorders |
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| coronary artery thrombosis | Cardiac disorders |
|
| papillary muscle rupture | Cardiac disorders |
|
| ventricular arrhythmia | Cardiac disorders |
|
| chest pain | General disorders |
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| multi-organ failure | General disorders |
|
| systemic inflammatory response syndrome | General disorders |
|
| abdominal sepsis | Infections and infestations |
|
| beta haemolytic streptococcal infection | Infections and infestations |
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| gastroenteritis norovirus | Infections and infestations |
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| mediastinitis | Infections and infestations |
|
| vasoplegia syndrome | Injury, poisoning and procedural complications |
|
| renal failure acute | Renal and urinary disorders |
|
| bronchospasm | Respiratory, thoracic and mediastinal disorders |
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| hypoxia | Respiratory, thoracic and mediastinal disorders |
|
| respiratory failure | Respiratory, thoracic and mediastinal disorders |
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| arterial thrombosis limb | Vascular disorders |
|
| overdose | Injury, poisoning and procedural complications |
|
| arthralgia | Musculoskeletal and connective tissue disorders |
|
| dyspnoea | Respiratory, thoracic and mediastinal disorders |
|
| atrial fibrillation | Cardiac disorders |
|
| pericardial effusion | Cardiac disorders |
|
| tachycardia | Cardiac disorders |
|
| ileus | Gastrointestinal disorders |
|
| nausea | Gastrointestinal disorders |
|
| toothache | Gastrointestinal disorders |
|
| discomfort | General disorders |
|
| pyrexia | General disorders |
|
| anemia postoperative | Injury, poisoning and procedural complications |
|
| incision site pain | Injury, poisoning and procedural complications |
|
| procedural hypotension | Injury, poisoning and procedural complications |
|
| white blood cell count increased | Investigations |
|
| fluid overload | Metabolism and nutrition disorders |
|
| back pain | Musculoskeletal and connective tissue disorders |
|
| lethargy | Nervous system disorders |
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| metabolic encephalopathy | Nervous system disorders |
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| agitation | Psychiatric disorders |
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| confusional state | Psychiatric disorders |
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| disorientation | Psychiatric disorders |
|
| restlessness | Psychiatric disorders |
|
| azotaemia | Renal and urinary disorders |
|
| bronchial secretion retention | Respiratory, thoracic and mediastinal disorders |
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| dyspnoea exertional | Respiratory, thoracic and mediastinal disorders |
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| respiratory distress | Respiratory, thoracic and mediastinal disorders |
|
| constipation | Gastrointestinal disorders |
|
| musculoskeletal pain | Musculoskeletal and connective tissue disorders |
|
| anxiety | Psychiatric disorders |
|
| insomnia | Psychiatric disorders |
|
| pleural effusion | Respiratory, thoracic and mediastinal disorders |
|
In general, PI communications regarding trial results are prohibited until after the communication and publication of the multi-center results by Sponsor, but no more than 12 months after conclusion of the trial at all sites.
PI must submit results communications to sponsor for review at least 60 days prior to submission for publication and Sponsor may embargo such communications for a period that is less than or equal to 150 days solely to seek appropriate patent protection.
| Following discontinuation of study drug infusion |
|
| GUSTO moderate |
|
| GUSTO mild |
|