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Trial record 18 of 27 for:    cangrelor

Maintenance of Platelet Inhibition With Cangrelor (Bridge)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00767507
Recruitment Status : Completed
First Posted : October 7, 2008
Results First Posted : April 4, 2014
Last Update Posted : April 4, 2014
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Coronary Syndrome (ACS)
Interventions Drug: cangrelor
Other: Placebo
Enrollment 221
Recruitment Details 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.
Pre-assignment Details

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.

Arm/Group Title Stage I, Cohort I - 0.5 mcg/kg/Min Cangrelor Stage I, Cohort II - 0.75 mcg/kg/Min Cangrelor Stage II - Cangrelor Arm (0.75 mcg/kg/Min ) Stage II - Placebo Arm
Hide Arm/Group Description 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. 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. 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. 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.
Period Title: Overall Study
Started 5 6 106 104
Completed 5 6 106 101
Not Completed 0 0 0 3
Arm/Group Title Stage I, Cohort I - 0.5 mcg/kg/Min Cangrelor Stage I, Cohort II - 0.75 mcg/kg/Min Cangrelor Stage II Cangrelor Arm (0.75 mcg/kg/Min) Stage II Placebo Arm Total
Hide Arm/Group Description 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. 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 5 6 106 101 218
Hide Baseline Analysis Population Description
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.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 6 participants 106 participants 101 participants 218 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
  60.0%
3
  50.0%
52
  49.1%
59
  58.4%
117
  53.7%
>=65 years
2
  40.0%
3
  50.0%
54
  50.9%
42
  41.6%
101
  46.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 6 participants 106 participants 101 participants 218 participants
Female
0
   0.0%
2
  33.3%
26
  24.5%
27
  26.7%
55
  25.2%
Male
5
 100.0%
4
  66.7%
80
  75.5%
74
  73.3%
163
  74.8%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 6 participants 106 participants 101 participants 218 participants
United States 5 6 66 59 136
Netherlands 0 0 5 6 11
Czech Republic 0 0 26 29 55
United Kingdom 0 0 8 4 12
Austria 0 0 1 6 7
[1]
Measure Description: 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.
1.Primary Outcome
Title 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.
Hide Description 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).
Time Frame During study drug infusion up to 1-6 hours prior to surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Stage I, Cohort I - Cangrelor 0.5 mcg/kg/Min Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 6
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
17 18
Measure Type: Number
Unit of Measure: percentage of samples
76.5 94.4
2.Primary Outcome
Title 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.
Hide Description

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.

Time Frame During study drug infusion up to 1-6 hours prior to surgery
Hide Outcome Measure Data
Hide Analysis Population Description

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).

Arm/Group Title Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm
Hide Arm/Group Description:
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.
Patients who received m as a 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.
Overall Number of Participants Analyzed 84 84
Measure Type: Number
Unit of Measure: Percent of patients
98.8 19.0
3.Secondary Outcome
Title Stage II: Analysis of Platelet Reactivity (ITT Population) / Patients With Platelet Reactivity < 240 PRU
Hide Description

This endpoint analyzed the percent of patients with platelet reactivity < 240 PRU at the following timepoints:

  • Baseline - Prior to study drug infusion (washout period from oral P2Y12 inhibition)
  • Last sample during infusion
  • Following discontinuation of study drug infusion
Time Frame baseline until just prior to surgery (post infusion)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 93 90
Measure Type: Number
Unit of Measure: percent of patients
Prior to study drug infusion (washout period) 62.4 52.3
Last sample during infusion 98.8 31.0
Following discontinuation of study drug infusion 26.9 20.0
4.Secondary Outcome
Title Incidence of Excessive Coronary Artery Bypass Graft (CABG)-Related Bleeding
Hide Description 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
Time Frame Randomization through Hospital discharge
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm Stage I, Cohort I - Cangrelor 0.5 mcg/kg/Min Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 102 96 5 6
Measure Type: Number
Unit of Measure: Patients
12 10 0 1
5.Secondary Outcome
Title Non-CABG (Preoperative) Bleeding - Protocol-defined GUSTO Severe/Life-threatening, Moderate and Mild
Hide Description [Not Specified]
Time Frame Randomization until start of CABG surgery
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Stage II - Cangrelor (0.75 mcg/kg/Min) Stage II - Placebo Arm Stage I, Cohort 1 - Cangrelor 0.5 mcg/kg/Min Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 102 96 5 6
Measure Type: Number
Unit of Measure: participants
GUSTO severe/life threatening 2 1 0 0
GUSTO moderate 10 4 0 2
GUSTO mild 8 5 1 1
6.Secondary Outcome
Title Patients With Blood Product Transfusions up to 7 Days After Surgery or Discharge, Whichever Was Sooner
Hide Description [Not Specified]
Time Frame Through 7 days or hospital discharge, whichever was sooner
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm Stage I, Cohort 1 - Cangrelor (0.5 mcg/kg/Min) Stage I - Cohort II - Cangrelor 0.75 mcg/kg/Min
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 106 101 5 6
Measure Type: Number
Unit of Measure: patients
34 35 1 4
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Stage I, Cohort I - Cangrelor 0.5 mcg/kg/Min Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm
Hide Arm/Group Description 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. 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. 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. 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.
All-Cause Mortality
Stage I, Cohort I - Cangrelor 0.5 mcg/kg/Min Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Stage I, Cohort I - Cangrelor 0.5 mcg/kg/Min Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)   0/6 (0.00%)   11/106 (10.38%)   9/101 (8.91%) 
Cardiac disorders         
angina pectoris  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
atrial fibrillation  0/5 (0.00%)  0/6 (0.00%)  0/106 (0.00%)  1/101 (0.99%) 
cardiac arrest  0/5 (0.00%)  0/6 (0.00%)  3/106 (2.83%)  1/101 (0.99%) 
cardiac asthma  0/5 (0.00%)  0/6 (0.00%)  0/106 (0.00%)  1/101 (0.99%) 
cardiac failure  0/5 (0.00%)  0/6 (0.00%)  0/106 (0.00%)  2/101 (1.98%) 
cardiogenic shock  0/5 (0.00%)  0/6 (0.00%)  4/106 (3.77%)  1/101 (0.99%) 
cardiopulmonary failure  0/5 (0.00%)  0/6 (0.00%)  0/106 (0.00%)  1/101 (0.99%) 
coronary artery thrombosis  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
papillary muscle rupture  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
ventricular arrhythmia  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
General disorders         
chest pain  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
multi-organ failure  0/5 (0.00%)  0/6 (0.00%)  0/106 (0.00%)  1/101 (0.99%) 
systemic inflammatory response syndrome  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
Infections and infestations         
abdominal sepsis  0/5 (0.00%)  0/6 (0.00%)  0/106 (0.00%)  1/101 (0.99%) 
beta haemolytic streptococcal infection  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
gastroenteritis norovirus  0/5 (0.00%)  0/6 (0.00%)  0/106 (0.00%)  1/101 (0.99%) 
mediastinitis  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
Injury, poisoning and procedural complications         
vasoplegia syndrome  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
Renal and urinary disorders         
renal failure acute  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
bronchospasm  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
hypoxia  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
respiratory failure  0/5 (0.00%)  0/6 (0.00%)  2/106 (1.89%)  1/101 (0.99%) 
Vascular disorders         
arterial thrombosis limb  0/5 (0.00%)  0/6 (0.00%)  1/106 (0.94%)  0/101 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stage I, Cohort I - Cangrelor 0.5 mcg/kg/Min Stage I, Cohort II - Cangrelor 0.75 mcg/kg/Min Stage II - Cangrelor Arm (0.75 mcg/kg/Min) Stage II - Placebo Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/5 (60.00%)   5/6 (83.33%)   27/106 (25.47%)   23/101 (22.77%) 
Cardiac disorders         
angina pectoris  0/5 (0.00%)  1/6 (16.67%)  3/106 (2.83%)  0/101 (0.00%) 
atrial fibrillation  0/5 (0.00%)  1/6 (16.67%)  1/106 (0.94%)  5/101 (4.95%) 
pericardial effusion  0/5 (0.00%)  1/6 (16.67%)  0/106 (0.00%)  2/101 (1.98%) 
tachycardia  0/5 (0.00%)  1/6 (16.67%)  1/106 (0.94%)  0/101 (0.00%) 
Gastrointestinal disorders         
ileus  0/5 (0.00%)  1/6 (16.67%)  0/106 (0.00%)  0/101 (0.00%) 
nausea  0/5 (0.00%)  1/6 (16.67%)  10/106 (9.43%)  3/101 (2.97%) 
toothache  1/5 (20.00%)  0/6 (0.00%)  0/106 (0.00%)  0/101 (0.00%) 
constipation  0/5 (0.00%)  0/6 (0.00%)  7/106 (6.60%)  2/101 (1.98%) 
General disorders         
discomfort  0/5 (0.00%)  1/6 (16.67%)  1/106 (0.94%)  0/101 (0.00%) 
pyrexia  1/5 (20.00%)  0/6 (0.00%)  1/106 (0.94%)  3/101 (2.97%) 
Injury, poisoning and procedural complications         
overdose  0/5 (0.00%)  0/6 (0.00%)  2/106 (1.89%)  5/101 (4.95%) 
anemia postoperative  0/5 (0.00%)  1/6 (16.67%)  1/106 (0.94%)  0/101 (0.00%) 
incision site pain  1/5 (20.00%)  1/6 (16.67%)  11/106 (10.38%)  8/101 (7.92%) 
procedural hypotension  0/5 (0.00%)  1/6 (16.67%)  1/106 (0.94%)  0/101 (0.00%) 
Investigations         
white blood cell count increased  0/5 (0.00%)  1/6 (16.67%)  0/106 (0.00%)  0/101 (0.00%) 
Metabolism and nutrition disorders         
fluid overload  0/5 (0.00%)  1/6 (16.67%)  3/106 (2.83%)  0/101 (0.00%) 
Musculoskeletal and connective tissue disorders         
arthralgia  0/5 (0.00%)  1/6 (16.67%)  0/106 (0.00%)  0/101 (0.00%) 
back pain  0/5 (0.00%)  1/6 (16.67%)  4/106 (3.77%)  3/101 (2.97%) 
musculoskeletal pain  0/5 (0.00%)  0/6 (0.00%)  6/106 (5.66%)  1/101 (0.99%) 
Nervous system disorders         
lethargy  0/5 (0.00%)  1/6 (16.67%)  0/106 (0.00%)  1/101 (0.99%) 
metabolic encephalopathy  0/5 (0.00%)  1/6 (16.67%)  0/106 (0.00%)  0/101 (0.00%) 
Psychiatric disorders         
agitation  0/5 (0.00%)  1/6 (16.67%)  3/106 (2.83%)  1/101 (0.99%) 
confusional state  0/5 (0.00%)  1/6 (16.67%)  1/106 (0.94%)  1/101 (0.99%) 
disorientation  0/5 (0.00%)  1/6 (16.67%)  2/106 (1.89%)  0/101 (0.00%) 
restlessness  0/5 (0.00%)  1/6 (16.67%)  3/106 (2.83%)  0/101 (0.00%) 
anxiety  0/5 (0.00%)  0/6 (0.00%)  7/106 (6.60%)  2/101 (1.98%) 
insomnia  0/5 (0.00%)  0/6 (0.00%)  6/106 (5.66%)  1/101 (0.99%) 
Renal and urinary disorders         
azotaemia  0/5 (0.00%)  2/6 (33.33%)  0/106 (0.00%)  0/101 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
dyspnoea  0/5 (0.00%)  2/6 (33.33%)  2/106 (1.89%)  0/101 (0.00%) 
bronchial secretion retention  0/5 (0.00%)  1/6 (16.67%)  0/106 (0.00%)  0/101 (0.00%) 
dyspnoea exertional  0/5 (0.00%)  1/6 (16.67%)  1/106 (0.94%)  0/101 (0.00%) 
respiratory distress  1/5 (20.00%)  0/6 (0.00%)  0/106 (0.00%)  0/101 (0.00%) 
pleural effusion  0/5 (0.00%)  0/6 (0.00%)  5/106 (4.72%)  9/101 (8.91%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Meredith Todd - Sr. Director Program Management
Organization: The Medicines Company
Phone: +1.973.290.6088
EMail: meredith.todd@themedco.com
Layout table for additonal information
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT00767507     History of Changes
Other Study ID Numbers: TMC-CAN-08-02
First Submitted: October 6, 2008
First Posted: October 7, 2008
Results First Submitted: April 23, 2013
Results First Posted: April 4, 2014
Last Update Posted: April 4, 2014