Blood Loss, SurgicalPhase 2NCT00448864
Efficacy Study of Recombinant Protein (Ecallantide) to Reduce Blood Loss During Primary Coronary Bypass Grafting or Valve Repair/Replacement
A Phase 2 study testing Ecallantide in people with Blood Loss, Surgical, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 15 sites in United States.
Trial summary
The primary objective of this study was to assess the efficacy and safety of 2 dose levels of ecallantide versus placebo in reducing blood loss following cardiopulmonary bypass (CPB), as measured by chest tube drainage during the first 12 hours postoperatively or until the chest tube was removed, whichever came first… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Blood Loss, Surgical
- What is being tested?
- Ecallantide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 15 sitesUnited States
- Study dates
- 1 May 2007to 1 Aug 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ≥18 to ≤85 years of age
- Elective primary coronary artery bypass grafting (CABG), single valve repair, or single valve replacement requiring CPB and full sternotomy
- No plan to use desmopressin acetate (DDAVP), atrial natriuretic hormone, E-aminocaproic acid (EACA), tranexamic acid, or aprotinin during or postoperatively
- Female participants must be non-lactating and not pregnant
- If of childbearing potential, female participants must agree to use adequate contraception for 1 month after receiving study drug
Who cannot join
- Concomitant surgery including but not limited to atrial septal defect repair, multiple valve replacement, carotid endarterectomy, and combined CABG and valve procedure
- Planned hypothermic CPB using temperatures less than 28 degrees Celsius
- Weight <55 kilograms (kg)
- Major end organ dysfunction, defined as:
- Cardiac:
- Left ventricular ejection fraction (LVEF) < 30% by left ventriculography, echocardiogram, or catheterization (within 90 days prior to screening)
Show all 31Show fewer
- Use of positive IV inotropic agents within 12 hours prior to surgery
- Preoperative use of intra-aortic balloon pump (IABP), left ventricular assist device (LVAD), or extracorporeal membrane oxygenation (ECMO)
- Renal: Serum creatinine > 1.5 milligrams per deciliter (mg/dL)
- Hepatic: Aspartate aminotransferase (AST) or alanine transferase (ALT) > 2.5 x upper limit normal
- Hematologic:
- Preoperative hematocrit (Hct) < 30%
- Platelet count < 100,000/mm^3
- Planned transfusion during surgical procedure
- History or family history of bleeding or clotting disorder (for example, von Willebrand's Disease, idiopathic thrombocytopenia purpura (ITP), thrombotic thrombocytopenia purpura (TTP), hematologic malignancy)
- Prothrombin time (PT) or activated partial thromboplastin time
- (aPTT) > 1.5 x normal range; if receiving unfractionated heparin preoperatively, then abnormal preoperative PT/aPTT permitted
- Serious intercurrent illness or active infection
- Previous exposure to ecallantide
- Known allergy to ecallantide or any of its components, fentanyl, midazolam, isoflurane, propofol, morphine, heparin, or protamine
- Autologous blood donation ≤ 30 days month prior to surgery
- Known substance abuse within 6 months prior to surgery
- Receipt of an investigational drug or device within 30 days prior to participation in the current study
- Administration of:
- Eptifibatide < 12 hours prior to surgery
- Tirofiban hydrochloride (HCl) < 12 hours prior to surgery
- Enoxaparin sodium or other low- molecular-weight heparin < 24 hours prior to surgery
- Clopidogrel <5 days prior to surgery
- Warfarin <5 days prior to surgery (Warfarin must be discontinued 5 days prior to surgery and PT must be < 18 seconds)
- Ticlopidine <7 days prior to surgery
- Abciximab <24 hours prior to surgery
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
University of Colorado
Aurora, Colorado, 80045
St. Vincent's Hospital
Birmingham, Alabama, 35205
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Caritas St. Elizabeth's Medical Center
Boston, Massachusetts, 02135
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Cleveland Clinic
Cleveland, Ohio, 44195
Duke University Medical Center
Durham, North Carolina, 27710
Gaston Memorial Hospital
Gastonia, North Carolina, 28054
The Methodist Hospital
Houston, Texas, 77030
Texas Heart Institute
Houston, Texas, 77225
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic Hospital
Phoenix, Arizona, 85054
Mayo Clinic
Rochester, Minnesota, 55905
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
Official title: KALAHARI-1: Kallikrein Antagonist (DX-88 [Ecallantide]) Effect on Blood Loss Associated With Heart Surgery Requiring Institution of Bypass
The primary objective of this study was to assess the efficacy and safety of 2 dose levels of ecallantide versus placebo in reducing blood loss following cardiopulmonary bypass (CPB), as measured by chest tube drainage during the first 12 hours postoperatively or until the chest tube was removed, whichever came first, in patients undergoing primary coronary artery bypass grafting (CABG), single valve repair, or single valve replacement.
The secondary objective was to compare the efficacy of all ecallantide-treated participants (pooled high and low-doses) to placebo and to compare the high-dose to the low-dose ecallantide group. Other secondary objectives were to evaluate pharmacokinetics and antibody formation.
Read the detailed description
This was a Phase 2, randomized, double-blind, placebo-controlled, multi-center study designed to assess the efficacy and safety of 2 dose levels of ecallantide compared to placebo in reducing chest tube drainage in participants requiring CPB for primary CABG, single valve repair, or single valve replacement. Participants were randomized in a 3:3:2 ratio to ecallantide high-dose regimen (maximum 91 mg), ecallantide low-dose regimen (maximum 15 mg), or placebo. Randomization was stratified by surgical procedure so that participants undergoing valve replacement would be evenly distributed across treatment arms. Each participant received active drug or placebo administered in stages on the day of the surgical procedure after induction of anesthesia (Day 1).
Participants were screened up to 14 days prior to surgery. Additional study procedures were conducted on Day -1 or 1, peri-operatively, during the immediate postoperative period, and on Days 2, 4, and 7 (or at the time of discharge from the hospital), and between Days 28 and 43 (follow-up).
- Conditions
- Blood Loss, Surgical
- Being tested
- Ecallantide, Placebo
- Medical subject headings
- Blood Loss, Surgical
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EcallantideDrug
Also called DX-88
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Ecallantide - Low Dose Regimen | Experimental | Participants received a maximum of 15 milligrams (mg) ecallantide in stages. Intravenous (IV) infusion of 0.6 milligrams per milliliter (mg/mL) ecallantide was administered at 2.92 milliliters per minute (mL/min) for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of cardiopulmonary bypass (CPB), whichever came first. At the termination of the initial infusion, a second infusion of 0.4 mg/mL ecallantide was started at 38 milliliters per hour (mL/hr) for 4 hours. Receives: Drug: Ecallantide |
| Ecallantide - High Dose Regimen | Experimental | Participants received a maximum of 91 mg ecallantide in stages. IV infusion of 0.6 mg/mL ecallantide was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, an infusion of normal saline was started at 38 milliliters per hour (mL/hr) for 4 hours. Receives: Drug: Ecallantide |
| Placebo | Placebo comparator | Participants received placebo in stages. IV infusion placebo was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, a second infusion of placebo was started at 38 mL/hr for 4 hours. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Chest Tube Drainage During the First 12 Hours Postoperatively
Mean volume of chest tube drainage during the first 12 hours postoperatively or until chest tube removal, whichever occurred first, is presented for each treatment group.
Measured: Up to 12 hours post admission to intensive care unit (ICU)
Secondary outcomes (3)
Cumulative Chest Tube Drainage at 24 Hours Postoperatively
Mean volume of chest tube drainage during the first 24 hours postoperatively or until chest tube removal, whichever occurred first, is presented for each treatment group.
Measured: Up to 24 hours post admission to ICU
Number of Participants With Treatment-emergent Adverse Events
A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Measured: up to 28 days post admission to ICU
Pharmacokinetics: Area Under the Concentration Time Curve
Results are reported in terms of the Area Under Plasma Concentration Time Curve (AUC), measured as milligram hour per liter (mg*h/L)
Measured: 1, 2, 4, and 8 hours after end of study drug infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2007 (estimated)
- Study start1 May 2007
- Primary completion1 Jul 2008
- Study completion1 Aug 2008
Why it stopped: Experience gained from this study is sufficient to design and facilitate the follow-on study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Blood Loss, SurgicalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andrew L Sternlicht, MD, Study director, Dyax Corp.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00448864
- Sponsor's protocol ID
- 1501-001
- Other IDs
- DX-88/16
- Status last verified
- Jun 2019
- First submitted
- 16 Mar 2007
- Last updated
- 25 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KALAHARI-1: Kallikrein Antagonist (DX-88 [Ecallantide]) Effect on Blood Loss Associated With Heart Surgery Requiring Institution of Bypass
- ClinicalTrials.gov ID
- NCT00448864
- Acronym / sponsor ID
- 1501-001
- Conditions
- Blood Loss, Surgical
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Experience gained from this study is sufficient to design and facilitate the follow-on study.
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 1 May 2007 (actual)
- Primary completion
- 1 Jul 2008 (actual)
- Study completion
- 1 Aug 2008 (actual)
- First posted
- 19 Mar 2007 (estimated)
- Results
- Posted 8 Jul 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study was to assess the efficacy and safety of 2 dose levels of ecallantide versus placebo in reducing blood loss following cardiopulmonary bypass (CPB), as measured by chest tube drainage during the first 12 hours postoperatively or until the chest tube was removed, whichever came first, in patients undergoing primary coronary artery bypass grafting (CABG), single valve repair, or single valve replacement.
The secondary objective was to compare the efficacy of all ecallantide-treated participants (pooled high and low-doses) to placebo and to compare the high-dose to the low-dose ecallantide group. Other secondary objectives were to evaluate pharmacokinetics and antibody formation.
Detailed description
This was a Phase 2, randomized, double-blind, placebo-controlled, multi-center study designed to assess the efficacy and safety of 2 dose levels of ecallantide compared to placebo in reducing chest tube drainage in participants requiring CPB for primary CABG, single valve repair, or single valve replacement. Participants were randomized in a 3:3:2 ratio to ecallantide high-dose regimen (maximum 91 mg), ecallantide low-dose regimen (maximum 15 mg), or placebo. Randomization was stratified by surgical procedure so that participants undergoing valve replacement would be evenly distributed across treatment arms. Each participant received active drug or placebo administered in stages on the day of the surgical procedure after induction of anesthesia (Day 1).
Participants were screened up to 14 days prior to surgery. Additional study procedures were conducted on Day -1 or 1, peri-operatively, during the immediate postoperative period, and on Days 2, 4, and 7 (or at the time of discharge from the hospital), and between Days 28 and 43 (follow-up).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ecallantide - Low Dose Regimen | Experimental | Drug: EcallantideParticipants received a maximum of 15 milligrams (mg) ecallantide in stages. Intravenous (IV) infusion of 0.6 milligrams per milliliter (mg/mL) ecallantide was administered at 2.92 milliliters per minute (mL/min) for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of cardiopulmonary bypass (CPB), whichever came first. At the termination of the initial infusion, a second infusion of 0.4 mg/mL ecallantide was started at 38 milliliters per hour (mL/hr) for 4 hours. |
| Ecallantide - High Dose Regimen | Experimental | Drug: EcallantideParticipants received a maximum of 91 mg ecallantide in stages. IV infusion of 0.6 mg/mL ecallantide was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, an infusion of normal saline was started at 38 milliliters per hour (mL/hr) for 4 hours. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo in stages. IV infusion placebo was administered at 2.92 mL/min for 20 minutes. The infusion rate was then reduced to 0.583 mL/min for 160 minutes, or until the end of CPB, whichever came first. At the termination of the initial infusion, a second infusion of placebo was started at 38 mL/hr for 4 hours. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women ≥18 to ≤85 years of age
- Elective primary coronary artery bypass grafting (CABG), single valve repair, or single valve replacement requiring CPB and full sternotomy
- No plan to use desmopressin acetate (DDAVP), atrial natriuretic hormone, E-aminocaproic acid (EACA), tranexamic acid, or aprotinin during or postoperatively
- Female participants must be non-lactating and not pregnant
- If of childbearing potential, female participants must agree to use adequate contraception for 1 month after receiving study drug
Key exclusion criteria (31 listed)
- Concomitant surgery including but not limited to atrial septal defect repair, multiple valve replacement, carotid endarterectomy, and combined CABG and valve procedure
- Planned hypothermic CPB using temperatures less than 28 degrees Celsius
- Weight <55 kilograms (kg)
- Major end organ dysfunction, defined as:
- Serious intercurrent illness or active infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EcallantideAlso: DX-88 | Drug | Ecallantide - High Dose Regimen, Ecallantide - Low Dose Regimen |
| Placebo | Drug | Placebo |
Primary outcome
Cumulative Chest Tube Drainage During the First 12 Hours Postoperatively
Time frame: Up to 12 hours post admission to intensive care unit (ICU)
Mean volume of chest tube drainage during the first 12 hours postoperatively or until chest tube removal, whichever occurred first, is presented for each treatment group.
3 secondary outcomes
Cumulative Chest Tube Drainage at 24 Hours Postoperatively
Time frame: Up to 24 hours post admission to ICU
Number of Participants With Treatment-emergent Adverse Events
Time frame: up to 28 days post admission to ICU
Pharmacokinetics: Area Under the Concentration Time Curve
Time frame: 1, 2, 4, and 8 hours after end of study drug infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew L Sternlicht, MD study director
Dyax Corp.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ecallantide in people with Blood Loss, Surgical, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative Chest Tube Drainage During the First 12 Hours Postoperatively (time frame: Up to 12 hours post admission to intensive care unit (ICU)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2019.