Trial Outcomes & Findings for Outcomes and Safety Trial Investigating Ecallantide's Effect on Reducing Surgical Blood Loss Volume in Subjects at High Risk of Bleeding Exposed to Cardio-pulmonary Bypass During Cardiac Surgery (NCT NCT00888940)

NCT ID: NCT00888940

Last Updated: 2015-08-10

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

243 participants

Primary outcome timeframe

12 hours after the end of surgery

Results posted on

2015-08-10

Participant Flow

Participant milestones

Participant milestones
Measure
Ecallantide
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron(R)
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Overall Study
STARTED
120
122
Overall Study
Completed Therapy
107
106
Overall Study
COMPLETED
92
101
Overall Study
NOT COMPLETED
28
21

Reasons for withdrawal

Reasons for withdrawal
Measure
Ecallantide
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron(R)
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Overall Study
Adverse Event
12
3
Overall Study
Lost to Follow-up
5
5
Overall Study
Randomized Not Treated
11
13

Baseline Characteristics

Outcomes and Safety Trial Investigating Ecallantide's Effect on Reducing Surgical Blood Loss Volume in Subjects at High Risk of Bleeding Exposed to Cardio-pulmonary Bypass During Cardiac Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ecallantide
n=120 Participants
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron(R)
n=122 Participants
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Total
n=242 Participants
Total of all reporting groups
Age, Continuous
69.6 years
STANDARD_DEVIATION 8.02 • n=5 Participants
66.9 years
STANDARD_DEVIATION 10.88 • n=7 Participants
68.2 years
STANDARD_DEVIATION 9.65 • n=5 Participants
Sex: Female, Male
Female
45 Participants
n=5 Participants
50 Participants
n=7 Participants
95 Participants
n=5 Participants
Sex: Female, Male
Male
75 Participants
n=5 Participants
72 Participants
n=7 Participants
147 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
120 Participants
n=5 Participants
122 Participants
n=7 Participants
242 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 12 hours after the end of surgery

Population: Modified Intent to Treat = all subjects received at least one dose and analyzed according to planned treatment assignment. 3 subjects in ecallantide group not included due to no value being present

Outcome measures

Outcome measures
Measure
Ecallantide
n=106 Participants
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron(R)
n=109 Participants
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Cumulative Volume of Packed Red Blood Cells Transfused
1223.2 mL
Standard Deviation 1334.57
623.5 mL
Standard Deviation 974.64

SECONDARY outcome

Timeframe: Over the duration of the study.

Population: Safety population analyzed

Outcome measures

Outcome measures
Measure
Ecallantide
n=109 Participants
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron(R)
n=109 Participants
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Treatment-emergent Adverse Events.
At Least 1 TEAE
100 events
94 events
Treatment-emergent Adverse Events.
At Least 1 Related TEAE
5 events
5 events
Treatment-emergent Adverse Events.
At Least 1 Severe TEAE
38 events
17 events
Treatment-emergent Adverse Events.
At Least 1 Serious TEAE
45 events
28 events
Treatment-emergent Adverse Events.
At Least 1 Related & Serious TEAE
4 events
1 events
Treatment-emergent Adverse Events.
Premature Study Drug Discontinuations Due to TEAE
2 events
2 events
Treatment-emergent Adverse Events.
Related TEAE Resulting in Discontinuation of Drug
0 events
0 events
Treatment-emergent Adverse Events.
TEAE Resulting in Death
13 events
4 events
Treatment-emergent Adverse Events.
Related TEAE Resulting in Death
0 events
0 events

Adverse Events

Ecallantide

Serious events: 45 serious events
Other events: 93 other events
Deaths: 0 deaths

Cyklokapron

Serious events: 28 serious events
Other events: 91 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ecallantide
n=109 participants at risk
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron
n=109 participants at risk
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Blood and lymphatic system disorders
Anaemia
0.00%
0/109
0.92%
1/109 • Number of events 1
Blood and lymphatic system disorders
Coagulopathy
0.00%
0/109
0.92%
1/109 • Number of events 1
Cardiac disorders
Aortic valve incompetence
0.00%
0/109
0.92%
1/109 • Number of events 1
Cardiac disorders
Atrial fibrillation
1.8%
2/109 • Number of events 2
0.92%
1/109 • Number of events 1
Cardiac disorders
Atrioventricular block complete
1.8%
2/109 • Number of events 2
0.92%
1/109 • Number of events 1
Cardiac disorders
Bradycardia
0.92%
1/109 • Number of events 1
0.00%
0/109
Cardiac disorders
Cardiac arrest
3.7%
4/109 • Number of events 4
0.00%
0/109
Cardiac disorders
Cardiac failure
2.8%
3/109 • Number of events 3
0.92%
1/109 • Number of events 1
Cardiac disorders
Cardiac tamponade
3.7%
4/109 • Number of events 4
2.8%
3/109 • Number of events 3
Cardiac disorders
Cardio-respiratory arrest
0.00%
0/109
0.92%
1/109 • Number of events 1
Cardiac disorders
Cardiogenic shock
1.8%
2/109 • Number of events 2
0.92%
1/109 • Number of events 1
Cardiac disorders
Left ventricular failure
0.92%
1/109 • Number of events 1
0.00%
0/109
Cardiac disorders
Mitral valve incompetence
0.00%
0/109
0.92%
1/109 • Number of events 1
Cardiac disorders
Myocardial infarction
0.92%
1/109 • Number of events 1
0.00%
0/109
Cardiac disorders
Myocardial ischaemia
0.92%
1/109 • Number of events 1
0.00%
0/109
Cardiac disorders
Right ventricular failure
0.92%
1/109 • Number of events 1
0.00%
0/109
Cardiac disorders
Sick sinus syndrome
0.92%
1/109 • Number of events 1
0.00%
0/109
Cardiac disorders
Ventricle rupture
3.7%
4/109 • Number of events 4
0.00%
0/109
Cardiac disorders
Ventricular extrasystoles
0.00%
0/109
0.92%
1/109 • Number of events 1
Cardiac disorders
Ventricular fibrillation
3.7%
4/109 • Number of events 4
0.00%
0/109
Cardiac disorders
Ventricular hypokinesia
0.92%
1/109 • Number of events 1
0.00%
0/109
Cardiac disorders
Ventricular tachycardia
0.00%
0/109
0.92%
1/109 • Number of events 1
Gastrointestinal disorders
Gastrointestinal haemorrhage
1.8%
2/109 • Number of events 2
0.00%
0/109
Gastrointestinal disorders
Gastrointestinal necrosis
0.00%
0/109
0.92%
1/109 • Number of events 1
Gastrointestinal disorders
Pancreatic necrosis
0.00%
0/109
0.92%
1/109 • Number of events 1
General disorders
Impaired healing
1.8%
2/109 • Number of events 2
0.92%
1/109 • Number of events 1
General disorders
Multi-organ failure
2.8%
3/109 • Number of events 3
1.8%
2/109 • Number of events 2
Hepatobiliary disorders
Cholecystitis
0.00%
0/109
0.92%
1/109 • Number of events 1
Hepatobiliary disorders
Hyperbilirubinaemia
0.92%
1/109 • Number of events 1
0.00%
0/109
Infections and infestations
Bronchopneumonia
0.00%
0/109
0.92%
1/109 • Number of events 1
Infections and infestations
Pneumonia
0.00%
0/109
0.92%
1/109 • Number of events 1
Infections and infestations
Postoperative wound infection
0.92%
1/109 • Number of events 1
0.00%
0/109
Infections and infestations
Pseudomembranous colitis
0.92%
1/109 • Number of events 1
0.00%
0/109
Infections and infestations
Sepsis
0.92%
1/109 • Number of events 1
0.92%
1/109 • Number of events 1
Infections and infestations
Septic shock
0.00%
0/109
0.92%
1/109 • Number of events 1
Infections and infestations
Staphylococcal infection
0.92%
1/109 • Number of events 1
0.00%
0/109
Infections and infestations
Staphylococcal sepsis
0.92%
1/109 • Number of events 1
0.00%
0/109
Infections and infestations
Stenotrophomonas infection
0.92%
1/109 • Number of events 1
0.00%
0/109
Infections and infestations
Wound infection
0.00%
0/109
1.8%
2/109 • Number of events 2
Injury, poisoning and procedural complications
Post procedural complication
0.92%
1/109 • Number of events 1
0.92%
1/109 • Number of events 1
Injury, poisoning and procedural complications
Post procedural haemorrhage
10.1%
11/109 • Number of events 13
6.4%
7/109 • Number of events 7
Injury, poisoning and procedural complications
Postoperative thoracic procedure complication
2.8%
3/109 • Number of events 3
0.00%
0/109
Injury, poisoning and procedural complications
Vasoplegia syndrome
0.92%
1/109 • Number of events 1
0.00%
0/109
Investigations
Cardiac output decreased
1.8%
2/109 • Number of events 2
0.00%
0/109
Nervous system disorders
Cerebral haemorrhage
0.92%
1/109 • Number of events 1
0.00%
0/109
Nervous system disorders
Cerebrovascular accident
0.00%
0/109
1.8%
2/109 • Number of events 2
Nervous system disorders
Convulsion
0.00%
0/109
0.92%
1/109 • Number of events 1
Nervous system disorders
Hypoxic encephalopathy
1.8%
2/109 • Number of events 2
0.00%
0/109
Nervous system disorders
Neurological decompensation
0.92%
1/109 • Number of events 1
0.00%
0/109
Psychiatric disorders
Impaired self-care
0.92%
1/109 • Number of events 1
0.00%
0/109
Renal and urinary disorders
Renal failure
1.8%
2/109 • Number of events 2
1.8%
2/109 • Number of events 2
Renal and urinary disorders
Renal failure acute
0.92%
1/109 • Number of events 1
0.92%
1/109 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
0.00%
0/109
0.92%
1/109 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Apnoea
0.92%
1/109 • Number of events 1
0.00%
0/109
Respiratory, thoracic and mediastinal disorders
Pneumothorax
1.8%
2/109 • Number of events 2
0.92%
1/109 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
0.00%
0/109
0.92%
1/109 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Respiratory failure
4.6%
5/109 • Number of events 5
3.7%
4/109 • Number of events 4
Vascular disorders
Air embolism
0.92%
1/109 • Number of events 1
0.00%
0/109
Vascular disorders
Haemorrhage
8.3%
9/109 • Number of events 9
0.00%
0/109
Vascular disorders
Hypotension
0.00%
0/109
0.92%
1/109 • Number of events 1
Vascular disorders
Peripheral ischaemia
0.92%
1/109 • Number of events 1
0.00%
0/109

Other adverse events

Other adverse events
Measure
Ecallantide
n=109 participants at risk
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron
n=109 participants at risk
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime
Blood and lymphatic system disorders
Anaemia
16.5%
18/109 • Number of events 18
14.7%
16/109 • Number of events 17
Cardiac disorders
Arrhythmia
6.4%
7/109 • Number of events 7
4.6%
5/109 • Number of events 5
Cardiac disorders
Atrial fibrillation
29.4%
32/109 • Number of events 32
17.4%
19/109 • Number of events 20
Cardiac disorders
Tachycardia
2.8%
3/109 • Number of events 3
8.3%
9/109 • Number of events 9
Gastrointestinal disorders
Constipation
8.3%
9/109 • Number of events 9
9.2%
10/109 • Number of events 10
Gastrointestinal disorders
Diarrhoea
3.7%
4/109 • Number of events 4
7.3%
8/109 • Number of events 8
Gastrointestinal disorders
Nausea
5.5%
6/109 • Number of events 6
8.3%
9/109 • Number of events 9
Gastrointestinal disorders
Vomiting
6.4%
7/109 • Number of events 8
3.7%
4/109 • Number of events 4
General disorders
Impaired healing
5.5%
6/109 • Number of events 6
8.3%
9/109 • Number of events 9
General disorders
Non-cardiac chest pain
6.4%
7/109 • Number of events 9
8.3%
9/109 • Number of events 10
General disorders
Oedema peripheral
5.5%
6/109 • Number of events 6
6.4%
7/109 • Number of events 7
Injury, poisoning and procedural complications
Procedural pain
15.6%
17/109 • Number of events 18
22.9%
25/109 • Number of events 25
Metabolism and nutrition disorders
Hyperglycaemia
10.1%
11/109 • Number of events 11
13.8%
15/109 • Number of events 15
Psychiatric disorders
Sleep disorder
4.6%
5/109 • Number of events 5
5.5%
6/109 • Number of events 7
Psychiatric disorders
Transient psychosis
6.4%
7/109 • Number of events 7
3.7%
4/109 • Number of events 4
Renal and urinary disorders
Renal failure
2.8%
3/109 • Number of events 3
7.3%
8/109 • Number of events 8
Respiratory, thoracic and mediastinal disorders
Pleural effusion
13.8%
15/109 • Number of events 15
15.6%
17/109 • Number of events 17
Skin and subcutaneous tissue disorders
Decubitus ulcer
1.8%
2/109 • Number of events 2
5.5%
6/109 • Number of events 6
Vascular disorders
Hypertension
5.5%
6/109 • Number of events 6
9.2%
10/109 • Number of events 10
Vascular disorders
Hypotension
18.3%
20/109 • Number of events 20
18.3%
20/109 • Number of events 20

Additional Information

Alistair Wheeler, MD MFPM, Senior Director Clinical Research

Cubist Pharmaceuticals, Inc.

Phone: 781-860-8660

Results disclosure agreements

  • Principal investigator is a sponsor employee The first publication is initiated by Cubist. If the First Publication is not published within 1 year of Study conclusion or termination, Investigator shall have the right to publish and disclose the Data. Prior to any submission for publication, presentation, or communication of results or information arising from the Study, Investigator shall provide Cubist at least 90 days for review and comment upon the manuscript or other material for such publication or presentation.
  • Publication restrictions are in place

Restriction type: OTHER