CONSERV-1: A Dose-ranging Safety and Efficacy Study of Ecallantide to Reduce Surgical Blood Loss Volume
Sponsor
Cubist Pharmaceuticals LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00816023
Collaborator
(none)
276
29
4
10.1
9.5
0.9
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy and identify the optimal dose(s) of ecallantide in reducing blood loss in subjects undergoing coronary artery bypass surgery including the use of cardio pulmonary bypass.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
276 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
CONSERV-1 (Clinical Outcomes and Safety Trial to Investigate Ecallantide's Effect on Reducing Surgical Blood Loss Volume) A Phase 2 Randomized Placebo-controlled Dose-ranging Study in Subjects Exposed to Cardio-pulmonary Bypass During Primary Coronary Artery Bypass Graft Surgery
Study Start Date
:
Mar 1, 2009
Actual Primary Completion Date
:
Dec 1, 2009
Actual Study Completion Date
:
Jan 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ecallantide Low Dose target steady state concentration of 0.15 mg/L |
Drug: ecallantide
infusion administered IV over the duration of the surgical procedure
|
| Experimental: Ecallantide Medium Dose target steady state concentration of 0.75 mg/L |
Drug: ecallantide
infusion administered IV over the duration of the surgical procedure
|
| Experimental: Ecallantide High Dose target steady state concentration of 2.25 mg/L |
Drug: ecallantide
infusion administered IV over the duration of the surgical procedure
|
| Placebo Comparator: Placebo placebo |
Drug: placebo
solution for IV infusion over the duration of the surgical>> procedure
|
Outcome Measures
Primary Outcome Measures
- Cumulative Volume of Packed Red Blood Cells Transfused at 12 Hours Post Surgery [Start of surgery up to 12 hours after the end of surgery]
Secondary Outcome Measures
- Treatment-emergent Adverse Events [Over the duration of the study.]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Written informed consent (by study subject or appropriate legal representative) prior to any study-related procedure not part of normal medical care
-
Planned primary CABG surgery including the use of cardio-pulmonary bypass.
Exclusion Criteria:
-
Planned concomitant surgery including ASD repair, valve replacement, carotid endarterectomy, CABG combined procedures or any repeat sternotomy;
-
Body weight <55 kg;
-
Planned hypothermia (<28ºC);
-
Planned transfusion in the peri-operative or post-operative periods;
-
Planned transfusion of pre-operatively donated autologous blood;
-
Female subjects who are pregnant or lactating;
-
Planned use of desmopressin, lysine analogs, atrial natriuretic hormone or recombinant activated Factor VII;
-
Planned use of corticosteroids in the pump prime solution;
-
Ejection fraction <30% within 90 days prior to surgery;
-
Evidence of a myocardial infarction within 5 days prior to surgery;
-
History of stroke or transient ischemic attack within 3 months prior to surgery;
-
Hypotension or heart failure requiring the use of inotropes or mechanical devices within 24 hours prior to surgery;
-
Serum creatinine >2.0 mg/dL within 48 hours prior to surgery;
-
Serum hepatic enzymes above 2.5 times the upper limit of normal for the applicable laboratory;
-
Hematocrit <32% within 48 hours prior to surgery;
-
Platelet count below the normal range for the applicable laboratory within 14 days prior to surgery;
-
History of, or family history of, bleeding or clotting disorder or thrombophilia;
-
History of heparin-induced thrombocytopenia;
-
Prothrombin time and/or activated partial thromboplastin time >1.5 X normal range;
-
Serious intercurrent illness or active infection;
-
Any previous exposure to ecallantide;
-
Receipt of an investigational drug or device 30 days prior to participation in the current study;
-
Known allergy to any agent expected to be used in the intra-operative or post-operative periods; and
-
Administration of: Eptifibatide within 6 hours prior to surgery, Tirofiban HCl within 6 hours prior to surgery, *Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery, Clopidogrel within 5 days prior to surgery, Ticlopidine within 7 days prior to surgery, Abciximab within 5 days prior to surgery, *Bivalirudin, argatroban or lepirudin within 6 hours prior to surgery, *Fondaparinux within 72 hours prior to surgery, Prasugrel within 10 days prior to surgery [*Prophylactic use permitted for the prevention of deep vein thrombosis.]
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cardio-Thoracic Surgeons PC | Birmingham | Alabama | United States | 35205 |
| 2 | Drug Research and Analysis Corporation | Montgomery | Alabama | United States | 36106 |
| 3 | University of Colorado - Denver | Aurora | Colorado | United States | 80045 |
| 4 | Pepin Heart Hospital & Kiran Patel Research Institute | Tampa | Florida | United States | 33613 |
| 5 | Indiana Ohio Heart | Fort Wayne | Indiana | United States | 46804 |
| 6 | University of Kentucky | Lexington | Kentucky | United States | 40536 |
| 7 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 8 | Caritas St. Elizabeth's Medical Center | Boston | Massachusetts | United States | 02135 |
| 9 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 10 | MCVI - Covenant Medical Center | Saginaw | Michigan | United States | 48601 |
| 11 | MCVI - St. Mary's of Michigan | Saginaw | Michigan | United States | 48601 |
| 12 | Mayo Clinic | Rochester | Minnesota | United States | 55901 |
| 13 | St. Luke's - Roosevelt Hospital Center | New York | New York | United States | 10025 |
| 14 | Weill Medical College of Cornell University | New York | New York | United States | 10065 |
| 15 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 16 | Integris Baptist Medical Center | Oklahoma City | Oklahoma | United States | 73112 |
| 17 | East Tennessee Cardiovascular Surgery Group | Knoxville | Tennessee | United States | 37920 |
| 18 | Texas Heart Institute | Houston | Texas | United States | 77030 |
| 19 | Sentara Heart Hospital | Norfolk | Virginia | United States | 23507 |
| 20 | Virginia Commonwealth University | Richmond | Virginia | United States | 23298 |
| 21 | Charleston Area Medical Center (CAMC) | Charleston | West Virginia | United States | 25304 |
| 22 | Foothills Medical Centre | Calgary | Alberta | Canada | T2N 2T9 |
| 23 | St. Boniface General Hospital | Winnipeg | Manitoba | Canada | R2H 2A6 |
| 24 | New Brunswick Heart Centre | Saint John | New Brunswick | Canada | E2L 4L2 |
| 25 | Hamilton Health Sciences | Hamilton | Ontario | Canada | L8L 5G4 |
| 26 | St. Michael's Hospital | Toronto | Ontario | Canada | M5B 18W |
| 27 | Toronto General Hospital | Toronto | Ontario | Canada | M5G 2C4 |
| 28 | Montreal Heart Institute | Montreal | Quebec | Canada | H1T 1C8 |
| 29 | Institut Universitaire de Cardiologie et de Pneumologie de Quebec (Hospital Laval) | Quebec | Canada | G1V 4G5 |
Sponsors and Collaborators
- Cubist Pharmaceuticals LLC
Investigators
- Study Director: Alistair Wheeler, MD, MFPM, Cubist Pharmaceuticals LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT00816023
Other Study ID Numbers:
- ECAL-PCPB-08-02
First Posted:
Dec 31, 2008
Last Update Posted:
Aug 11, 2015
Last Verified:
Jul 1, 2015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ecallantide Low Dose | Ecallantide Medium Dose | Ecallantide High Dose | Placebo |
|---|---|---|---|---|
| Arm/Group Description | target steady state concentration of 0.15 mg/L | target steady state concentration of 0.75 mg/L | target steady state concentration of 2.25 mg/L | |
| Period Title: Overall Study | ||||
| STARTED | 71 | 62 | 69 | 74 |
| Completed Therapy | 65 | 59 | 61 | 63 |
| COMPLETED | 62 | 56 | 60 | 62 |
| NOT COMPLETED | 9 | 6 | 9 | 12 |
Baseline Characteristics
| Arm/Group Title | Ecallantide Low Dose | Ecallantide Medium Dose | Ecallantide High Dose | Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | target steady state concentration of 0.15 mg/L | target steady state concentration of 0.75 mg/L | target steady state concentration of 2.25 mg/L | Total of all reporting groups | |
| Overall Participants | 71 | 62 | 69 | 74 | 276 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
63.1
(9.96)
|
63.9
(9.40)
|
63.2
(10.73)
|
63.6
(10.90)
|
63.4
(10.15)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
13
18.3%
|
15
24.2%
|
15
21.7%
|
11
14.9%
|
54
19.6%
|
| Male |
58
81.7%
|
47
75.8%
|
54
78.3%
|
63
85.1%
|
222
80.4%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
2
3.2%
|
2
2.9%
|
0
0%
|
4
1.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
5
7%
|
5
8.1%
|
5
7.2%
|
3
4.1%
|
18
6.5%
|
| White |
66
93%
|
54
87.1%
|
61
88.4%
|
71
95.9%
|
252
91.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
1.6%
|
1
1.4%
|
0
0%
|
2
0.7%
|
Outcome Measures
| Title | Cumulative Volume of Packed Red Blood Cells Transfused at 12 Hours Post Surgery |
|---|---|
| Description | |
| Time Frame | Start of surgery up to 12 hours after the end of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Modified Intent to Treat population was the basis of this analysis, defined as all randomized subjects who received any amount of study drug and analyzed according to the planned treatment assignment. |
| Arm/Group Title | Ecallantide Low Dose | Ecallantide Medium Dose | Ecallantide High Dose | Placebo |
|---|---|---|---|---|
| Arm/Group Description | target steady state concentration of 0.15 mg/L | target steady state concentration of 0.75 mg/L | target steady state concentration of 2.25 mg/L | |
| Measure Participants | 65 | 58 | 63 | 63 |
| Mean (Standard Deviation) [mL] |
401.9
(624.87)
|
383.1
(620.62)
|
410.3
(639.47)
|
377.6
(608.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ecallantide Low Dose, Ecallantide Medium Dose, Ecallantide High Dose, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.474 |
| Comments | ||
| Method | Jonckheere-Terpstra | |
| Comments | ||
| Title | Treatment-emergent Adverse Events |
|---|---|
| Description | |
| Time Frame | Over the duration of the study. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis conducted on Safety population, defined as all subjects randomized and received any study drug. Treatment groups are based on actual treatment received. |
| Arm/Group Title | Ecallantide Low Dose | Ecallantide Medium Dose | Ecallantide High Dose | Placebo |
|---|---|---|---|---|
| Arm/Group Description | target steady state concentration of 0.15 mg/L | target steady state concentration of 0.75 mg/L | target steady state concentration of 2.25 mg/L | |
| Measure Participants | 65 | 59 | 62 | 63 |
| At least 1 TEAE |
65
91.5%
|
59
95.2%
|
62
89.9%
|
63
85.1%
|
| At least 1 Treatment-related AE |
7
9.9%
|
9
14.5%
|
4
5.8%
|
7
9.5%
|
| At least 1 AE of Severe Intensity |
11
15.5%
|
13
21%
|
15
21.7%
|
16
21.6%
|
| At least 1 Treatment-emergent SAE |
15
21.1%
|
19
30.6%
|
19
27.5%
|
15
20.3%
|
| At least 1 Treatment-related SAE |
1
1.4%
|
3
4.8%
|
1
1.4%
|
1
1.4%
|
| TEAE Resulting on Discontinuation of Study Drug |
0
0%
|
0
0%
|
1
1.4%
|
0
0%
|
| TEAE Resulting in Death |
0
0%
|
1
1.6%
|
0
0%
|
0
0%
|
| Treatment-related TEAE Resulting in Death |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | ECALLANTIDE HIGH DOSE | ECALLANTIDE MEDIUM DOSE | ECALLANTIDE LOW DOSE | PLACEBO | ||||
| Arm/Group Description | Target steady state concentration of 2.25 mg/L | Target steady state concentration of 0.75 mg/L | Target steady state concentration of 0.15 mg/L | |||||
All Cause Mortality |
||||||||
| ECALLANTIDE HIGH DOSE | ECALLANTIDE MEDIUM DOSE | ECALLANTIDE LOW DOSE | PLACEBO | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| ECALLANTIDE HIGH DOSE | ECALLANTIDE MEDIUM DOSE | ECALLANTIDE LOW DOSE | PLACEBO | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/62 (30.6%) | 19/59 (32.2%) | 15/65 (23.1%) | 15/63 (23.8%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Atrial fibrillation | 3/62 (4.8%) | 3 | 3/59 (5.1%) | 3 | 2/65 (3.1%) | 2 | 4/63 (6.3%) | 4 |
| Atrial flutter | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 1/63 (1.6%) | 1 |
| Atrioventricular block complete | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Cardiac failure | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Cardiac failure congestive | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 2/63 (3.2%) | 2 |
| Cardiac tamponade | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Cardiogenic shock | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Intracardiac thrombus | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Myocardial infarction | 1/62 (1.6%) | 1 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Ventricular fibrillation | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Dysphagia | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Pancreatitis acute | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Small intestinal obstruction | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| General disorders | ||||||||
| Hyperthermia | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Non-cardiac chest pain | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Secretion discharge | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Infections and infestations | ||||||||
| Bronchitis | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Cellulitis | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 1/63 (1.6%) | 1 |
| Incision site cellulitis | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Pneumonia | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Post procedural cellulitis | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Postoperative wound infection | 2/62 (3.2%) | 2 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 2/63 (3.2%) | 2 |
| Respiratory tract infection | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Staphylococcal sepsis | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Urinary tract infection | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Drug toxicity | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Femoral nerve injury | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Post procedural haemorrhage | 6/62 (9.7%) | 6 | 4/59 (6.8%) | 4 | 6/65 (9.2%) | 6 | 3/63 (4.8%) | 3 |
| Vascular graft occlusion | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Nervous system disorders | ||||||||
| Cerebral infarction | 0/62 (0%) | 0 | 2/59 (3.4%) | 2 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Cerebrovascular accident | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Encephalopathy | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Syncope vasovagal | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Psychiatric disorders | ||||||||
| Psychotic disorder | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Renal failure | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Renal failure acute | 2/62 (3.2%) | 2 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory failure | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 1/63 (1.6%) | 1 |
| Non-cardiogenic pulmonary oedema | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Pleural effusion | 1/62 (1.6%) | 1 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 2/63 (3.2%) | 2 |
| Pneumonia aspiration | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Pulmonary embolism | 1/62 (1.6%) | 1 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Pulmonary oedema | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Respiratory distress | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Respiratory failure | 1/62 (1.6%) | 1 | 3/59 (5.1%) | 4 | 1/65 (1.5%) | 1 | 1/63 (1.6%) | 1 |
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/62 (0%) | 0 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Hypotension | 0/62 (0%) | 0 | 3/59 (5.1%) | 3 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Peripheral ischaemia | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| ECALLANTIDE HIGH DOSE | ECALLANTIDE MEDIUM DOSE | ECALLANTIDE LOW DOSE | PLACEBO | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 62/62 (100%) | 59/59 (100%) | 65/65 (100%) | 63/63 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 21/62 (33.9%) | 21 | 30/59 (50.8%) | 31 | 25/65 (38.5%) | 28 | 22/63 (34.9%) | 23 |
| Leukocytosis | 8/62 (12.9%) | 8 | 5/59 (8.5%) | 5 | 4/65 (6.2%) | 5 | 4/63 (6.3%) | 4 |
| Thrombocytopenia | 7/62 (11.3%) | 7 | 6/59 (10.2%) | 6 | 6/65 (9.2%) | 6 | 5/63 (7.9%) | 5 |
| Cardiac disorders | ||||||||
| Atrial fibrillation | 18/62 (29%) | 20 | 23/59 (39%) | 23 | 17/65 (26.2%) | 17 | 12/63 (19%) | 12 |
| Atrial flutter | 1/62 (1.6%) | 1 | 3/59 (5.1%) | 3 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Cardiomegaly | 3/62 (4.8%) | 3 | 3/59 (5.1%) | 3 | 1/65 (1.5%) | 1 | 1/63 (1.6%) | 1 |
| Pericarditis | 1/62 (1.6%) | 1 | 3/59 (5.1%) | 3 | 2/65 (3.1%) | 2 | 1/63 (1.6%) | 1 |
| Sinus tachycardia | 7/62 (11.3%) | 7 | 8/59 (13.6%) | 8 | 9/65 (13.8%) | 9 | 11/63 (17.5%) | 11 |
| Supraventricular extrasystoles | 0/62 (0%) | 0 | 3/59 (5.1%) | 3 | 0/65 (0%) | 0 | 1/63 (1.6%) | 1 |
| Tachycardia | 4/62 (6.5%) | 5 | 7/59 (11.9%) | 7 | 3/65 (4.6%) | 3 | 5/63 (7.9%) | 5 |
| Ventricular extrasystoles | 7/62 (11.3%) | 8 | 5/59 (8.5%) | 6 | 2/65 (3.1%) | 2 | 4/63 (6.3%) | 5 |
| Gastrointestinal disorders | ||||||||
| Constipation | 24/62 (38.7%) | 24 | 24/59 (40.7%) | 24 | 20/65 (30.8%) | 20 | 17/63 (27%) | 17 |
| Diarrhoea | 0/62 (0%) | 0 | 4/59 (6.8%) | 4 | 3/65 (4.6%) | 3 | 1/63 (1.6%) | 1 |
| Dyspepsia | 3/62 (4.8%) | 3 | 4/59 (6.8%) | 4 | 2/65 (3.1%) | 2 | 1/63 (1.6%) | 1 |
| Nausea | 31/62 (50%) | 31 | 22/59 (37.3%) | 23 | 30/65 (46.2%) | 30 | 29/63 (46%) | 29 |
| Vomiting | 8/62 (12.9%) | 9 | 5/59 (8.5%) | 5 | 5/65 (7.7%) | 5 | 2/63 (3.2%) | 2 |
| General disorders | ||||||||
| Asthenia | 1/62 (1.6%) | 1 | 5/59 (8.5%) | 5 | 3/65 (4.6%) | 3 | 1/63 (1.6%) | 1 |
| Chills | 6/62 (9.7%) | 6 | 4/59 (6.8%) | 4 | 4/65 (6.2%) | 4 | 3/63 (4.8%) | 3 |
| Generalised oedema | 22/62 (35.5%) | 22 | 22/59 (37.3%) | 23 | 17/65 (26.2%) | 17 | 16/63 (25.4%) | 17 |
| Non-cardiac chest pain | 1/62 (1.6%) | 1 | 3/59 (5.1%) | 3 | 2/65 (3.1%) | 2 | 1/63 (1.6%) | 1 |
| Oedema | 3/62 (4.8%) | 3 | 4/59 (6.8%) | 4 | 2/65 (3.1%) | 2 | 3/63 (4.8%) | 3 |
| Oedema peripheral | 7/62 (11.3%) | 7 | 6/59 (10.2%) | 6 | 8/65 (12.3%) | 8 | 8/63 (12.7%) | 8 |
| Pain | 5/62 (8.1%) | 6 | 3/59 (5.1%) | 3 | 5/65 (7.7%) | 7 | 1/63 (1.6%) | 1 |
| Pyrexia | 7/62 (11.3%) | 7 | 14/59 (23.7%) | 14 | 9/65 (13.8%) | 9 | 8/63 (12.7%) | 8 |
| Injury, poisoning and procedural complications | ||||||||
| Anaemia postoperative | 8/62 (12.9%) | 8 | 5/59 (8.5%) | 5 | 5/65 (7.7%) | 5 | 4/63 (6.3%) | 4 |
| Incision site pain | 18/62 (29%) | 20 | 18/59 (30.5%) | 19 | 14/65 (21.5%) | 17 | 19/63 (30.2%) | 19 |
| Post procedural complication | 0/62 (0%) | 0 | 3/59 (5.1%) | 3 | 2/65 (3.1%) | 2 | 4/63 (6.3%) | 4 |
| Post procedural discharge | 5/62 (8.1%) | 6 | 2/59 (3.4%) | 2 | 2/65 (3.1%) | 2 | 4/63 (6.3%) | 4 |
| Post procedural haemorrhage | 1/62 (1.6%) | 1 | 2/59 (3.4%) | 2 | 3/65 (4.6%) | 3 | 7/63 (11.1%) | 7 |
| Procedural nausea | 4/62 (6.5%) | 4 | 4/59 (6.8%) | 4 | 1/65 (1.5%) | 1 | 2/63 (3.2%) | 2 |
| Procedural pain | 42/62 (67.7%) | 43 | 36/59 (61%) | 36 | 44/65 (67.7%) | 44 | 37/63 (58.7%) | 37 |
| Investigations | ||||||||
| Blood calcium decreased | 1/62 (1.6%) | 1 | 3/59 (5.1%) | 3 | 1/65 (1.5%) | 1 | 2/63 (3.2%) | 2 |
| Blood creatinine increased | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 4/65 (6.2%) | 4 | 2/63 (3.2%) | 2 |
| Blood lactate dehydrogenase increased | 0/62 (0%) | 0 | 3/59 (5.1%) | 3 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Body temperature increased | 3/62 (4.8%) | 3 | 4/59 (6.8%) | 4 | 7/65 (10.8%) | 7 | 2/63 (3.2%) | 2 |
| Breath sounds abnormal | 2/62 (3.2%) | 2 | 3/59 (5.1%) | 3 | 1/65 (1.5%) | 1 | 3/63 (4.8%) | 3 |
| Urine output decreased | 4/62 (6.5%) | 4 | 8/59 (13.6%) | 8 | 5/65 (7.7%) | 5 | 5/63 (7.9%) | 5 |
| White blood cell count increased | 5/62 (8.1%) | 5 | 6/59 (10.2%) | 6 | 3/65 (4.6%) | 3 | 6/63 (9.5%) | 6 |
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 4/62 (6.5%) | 4 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 0/63 (0%) | 0 |
| Fluid overload | 3/62 (4.8%) | 3 | 4/59 (6.8%) | 4 | 5/65 (7.7%) | 5 | 1/63 (1.6%) | 1 |
| Hyperglycaemia | 27/62 (43.5%) | 28 | 24/59 (40.7%) | 24 | 23/65 (35.4%) | 23 | 28/63 (44.4%) | 28 |
| Hyperkalaemia | 4/62 (6.5%) | 4 | 3/59 (5.1%) | 4 | 4/65 (6.2%) | 4 | 1/63 (1.6%) | 1 |
| Hypervolaemia | 4/62 (6.5%) | 4 | 3/59 (5.1%) | 3 | 1/65 (1.5%) | 1 | 3/63 (4.8%) | 3 |
| Hypocalcaemia | 9/62 (14.5%) | 9 | 6/59 (10.2%) | 6 | 4/65 (6.2%) | 4 | 5/63 (7.9%) | 5 |
| Hypoglycaemia | 6/62 (9.7%) | 6 | 5/59 (8.5%) | 5 | 2/65 (3.1%) | 2 | 4/63 (6.3%) | 4 |
| Hypokalaemia | 6/62 (9.7%) | 6 | 9/59 (15.3%) | 9 | 7/65 (10.8%) | 7 | 12/63 (19%) | 12 |
| Hyponatraemia | 0/62 (0%) | 0 | 3/59 (5.1%) | 3 | 1/65 (1.5%) | 1 | 3/63 (4.8%) | 3 |
| Hypophosphataemia | 4/62 (6.5%) | 4 | 1/59 (1.7%) | 1 | 0/65 (0%) | 0 | 3/63 (4.8%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 1/62 (1.6%) | 1 | 5/59 (8.5%) | 6 | 3/65 (4.6%) | 3 | 3/63 (4.8%) | 3 |
| Nervous system disorders | ||||||||
| Dizziness | 1/62 (1.6%) | 1 | 3/59 (5.1%) | 3 | 3/65 (4.6%) | 3 | 2/63 (3.2%) | 2 |
| Headache | 0/62 (0%) | 0 | 3/59 (5.1%) | 3 | 5/65 (7.7%) | 5 | 1/63 (1.6%) | 1 |
| Psychiatric disorders | ||||||||
| Agitation | 5/62 (8.1%) | 6 | 3/59 (5.1%) | 3 | 5/65 (7.7%) | 5 | 3/63 (4.8%) | 3 |
| Anxiety | 2/62 (3.2%) | 2 | 3/59 (5.1%) | 4 | 9/65 (13.8%) | 9 | 7/63 (11.1%) | 7 |
| Confusional state | 6/62 (9.7%) | 6 | 3/59 (5.1%) | 3 | 8/65 (12.3%) | 8 | 4/63 (6.3%) | 4 |
| Insomnia | 5/62 (8.1%) | 5 | 9/59 (15.3%) | 9 | 12/65 (18.5%) | 12 | 7/63 (11.1%) | 7 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Atelectasis | 30/62 (48.4%) | 32 | 26/59 (44.1%) | 27 | 23/65 (35.4%) | 24 | 28/63 (44.4%) | 28 |
| Chronic obstructive pulmonary disease | 0/62 (0%) | 0 | 3/59 (5.1%) | 3 | 0/65 (0%) | 0 | 0/63 (0%) | 0 |
| Dyspnoea | 2/62 (3.2%) | 2 | 4/59 (6.8%) | 4 | 7/65 (10.8%) | 7 | 3/63 (4.8%) | 3 |
| Pleural effusion | 24/62 (38.7%) | 26 | 18/59 (30.5%) | 21 | 13/65 (20%) | 14 | 17/63 (27%) | 18 |
| Pneumothorax | 4/62 (6.5%) | 5 | 3/59 (5.1%) | 3 | 3/65 (4.6%) | 3 | 7/63 (11.1%) | 7 |
| Productive cough | 3/62 (4.8%) | 3 | 2/59 (3.4%) | 2 | 2/65 (3.1%) | 2 | 5/63 (7.9%) | 5 |
| Pulmonary congestion | 0/62 (0%) | 0 | 0/59 (0%) | 0 | 1/65 (1.5%) | 1 | 4/63 (6.3%) | 4 |
| Pulmonary oedema | 4/62 (6.5%) | 4 | 11/59 (18.6%) | 12 | 8/65 (12.3%) | 8 | 5/63 (7.9%) | 5 |
| Respiratory acidosis | 5/62 (8.1%) | 5 | 7/59 (11.9%) | 7 | 5/65 (7.7%) | 5 | 3/63 (4.8%) | 3 |
| Vascular disorders | ||||||||
| Haematoma | 1/62 (1.6%) | 1 | 0/59 (0%) | 0 | 4/65 (6.2%) | 5 | 1/63 (1.6%) | 3 |
| Hypertension | 8/62 (12.9%) | 8 | 8/59 (13.6%) | 8 | 10/65 (15.4%) | 10 | 7/63 (11.1%) | 7 |
| Hypotension | 24/62 (38.7%) | 25 | 25/59 (42.4%) | 26 | 28/65 (43.1%) | 31 | 17/63 (27%) | 17 |
Limitations/Caveats
Secondary efficacy variables were considered exploratory and, based on failure of the primary endpoint to meet statistical significance and early termination of the trial, are not presented.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Alistair Wheeler, MD, MFPM, Senior Director Clinical Research |
|---|---|
| Organization | Cubist Pharmaceuticals, Inc. |
| Phone | 781-860-8660 |
| awheeler@cubist.com |
Responsible Party:
Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT00816023
Other Study ID Numbers:
- ECAL-PCPB-08-02
First Posted:
Dec 31, 2008
Last Update Posted:
Aug 11, 2015
Last Verified:
Jul 1, 2015