BloodlossPhase 2CONSERV-2NCT00888940

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

A Phase 2 study testing Ecallantide and Cyklokapron(R) in people with Bloodloss and Surgical Procedures, Operative, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 34 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Bloodloss, Surgical Procedures, Operative
What is being tested?: Ecallantide and Cyklokapron(R)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 243 participants
Where: 34 sitesin 3 countries
Study dates: Jun 2009to Jan 2010
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

Written informed consent (by study subject) prior to any study-related procedure not part of normal medical care;
Male or female between the ages of 18 and 85 years old, inclusive; and
Planned cardiac surgery using cardio-pulmonary bypass, for one of the following procedures: any repeat sternotomy; surgery to repair or replace more than one valve; combined CABG plus repair or replacement of at least one valve
If female, subject is non-lactating, and is either:Not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;Of childbearing potential but is not pregnant as confirmed by negative pregnancy test at time of screening (based on the β-subunit of HCG), and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.

Who cannot join

Planned primary CABG, single valve repair or replacement surgery, or any off pump procedure;
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;

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Planned use of desmopressin, lysine analogs (other than study medication), 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 (aspartate aminotransferase or alanine aminotransferase) 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 (e.g. von Willebrand's Disease, idiopathic thrombocytopenia purpura) or thrombophilia such as anti-thrombin III deficiency or Factor V Leiden mutation;
History of heparin-induced thrombocytopenia;
Prothrombin time (PT) and/or activated partial thromboplastin time (aPTT) >1.5 X normal range unless subject received heparin within 24 hours of test;
Serious intercurrent illness or active infection (e.g. endocarditis, sepsis, active malignancy requiring treatment);
Any previous exposure to ecallantide;
Receipt of an investigational drug or device 30 days prior to participation in the current study;
Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study;
Inability to comply with the protocol for the duration of the 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 hydrochloride within 6 hours prior to surgery, (Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery), Prasugrel within 10 days prior to surgery, Clopidogrel within 3 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), Chlorpromazine within 7 days prior to surgery (Prophylactic use permitted for the prevention of deep vein thrombosis.)
Planned use of heparin bonded bypass circuits;
Known allergy or hypersensitivity to tranexamic acid or any of the other ingredients;
Disturbance of color sense;
Evidence of hematuria or any acute thromboses or thromboembolic diseases such as deep vein thrombosis, pulmonary embolism, or vertebral vein thrombosis.

Trial locations and contacts

34 sites in 3 countries.

Country

City, postcode or hospital

34 sites in 3 countries

Germany20 sites

Universitaetsklinikum Aachen AoeR
Aachen, 52074
Klinikum Augsburg
Augsburg, 86156
Herz- und Gefaesszentrum Bad Bevensen
Bad Bevensen, 29549
Universitaetsklinikum Bonn
Bonn, 53105
Klinik und Poliklinik fuer Herz- und Thoraxchirurgie der Universitaet zu Koeln
Cologne, 50937
St. Johannes Hospital
Dortmund, 44137
Herzzentrum Dresden GmbH Universitaetsklinik
Dresden, 01307
Universitaetsklinikum Erlangen
Erlangen, 91054
Universitaetsklinikum Frankfurt
Frankfurt, 60590
Universitaetsklinikum Freiburg
Freiburg im Breisgau, 79106
Universitaetsmedizin Goettingen
Göttingen, 37075
Universitaetsklinikum Halle (Saale)
Halle, 06120
Universitaeres Herzzentrum Hamburg GmbH
Hamburg, 20246
Universitaetsklinikum Heidelberg
Heidelberg, 69120
Herzzentrum Leipzig GmbH
Leipzig, 04289
Klinik fuer Herzchirurgie des Universitaetsklinikum SH
Lübeck, 23538
Klinikum der Stadt Ludwigshafen gGmbH
Ludwigshafen, 67063
Deutsches Herzzentrum Muenchen
Munich, 80636
HELIOS Klinik Wuppertal
Wuppertal, 42117
Universitaetsklinikum Wuerzburg
Würzburg, 97080

Other trials in Germany

Poland13 sites

Uniwersytecki Szpital Kliniczny w Bialymstoku
Bialystok, 15-276
Szpital Uniwersytecki im. Dr. Antoniego Jurasza w Bydgoszczy
Bydgoszcz, 85-094
Akademickie Centrum Kliniczne, Szpital AM w Gdansku
Gdansk, 80-952
Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
Katowice, 40-635
Krakowski Szpital Specjalistyczny im. Jana Pawla II
Krakow, 31-200
Uniwersytecki Szpital Kliniczny Nr. 3 im. Dr Seweryna Sterlinga
Lódz, 91-425
Katedra Chorób Serca AM, Szpital Miejski im. J Strusia
Poznan, 61-833
Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiej Akademii Medycznej
Szczecin, 70-111
Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON
Warsaw, 04-414
Instytut Kardiologii im. Prymasa Tysiclecia Stefana Kardynała Wyszyńskiego
Warsaw, 04-628
Samodzielny Publiczny Szpital Kliniczny nr 1 we Wroclawiu
Wroclaw, 50-369
4 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ, Centrum Chorób Serca
Wroclaw, 50-981
Slaskie Centrum Chorób Serca
Zabrze, 41-800

Other trials in Poland

United States1 site

Cardio-Thoracic Surgeons PC
Birmingham, Alabama, 35205

Other trials in United States

About this study

Official title: CONSERV - 2 (Clinical Outcomes and Safety Trial to Investigate Ecallantide's Effect on Reducing Surgical Blood Loss Volume) - A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding

A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding

Conditions: Bloodloss, Surgical Procedures, Operative
Being tested: Ecallantide, Cyklokapron(R)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EcallantideDrug
2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion
Cyklokapron(R)Drug
1000-mg loading dose followed by a continuous infusion of 400 mg/hr with an additional 500 mg added to the pump prime

Study groups in NCT00888940
Study group	Role	What they receive
ecallantide	Experimental	Not described Receives: Drug: Ecallantide
Cyklokapron(R)	Active comparator	Not described Receives: Drug: Cyklokapron(R)

What is being measured

The primary outcome is the main question the study is designed to answer.

Cumulative Volume of Packed Red Blood Cells Transfused
Measured: 12 hours after the end of surgery

Secondary outcomes (1)

Treatment-emergent Adverse Events.
Measured: Over the duration of the study.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2009Jan 2010

First posted28 Apr 2009 (estimated)
Study startJun 2009
Primary completionDec 2009
Study completionJan 2010

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for BloodlossStudies 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: 243 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00888940
Sponsor's protocol ID: ECAL-CCPB-08-07
Acronym: CONSERV-2
Status last verified: Jul 2015
First submitted: 26 Apr 2009
Last updated: 10 Aug 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Bokesch PM, Szabo G, Wojdyga R, Grocott HP, Smith PK, Mazer CD, Vetticaden S, Wheeler A, Levy JH. A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial). J Thorac Cardiovasc Surg. 2012 May;143(5):1022-9. doi: 10.1016/j.jtcvs.2011.06.001. Epub 2011 Jul 2.
PubMed 21724197

Study at a glance

From the registry record, last updated by the sponsor on 10 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: CONSERV - 2 (Clinical Outcomes and Safety Trial to Investigate Ecallantide's Effect on Reducing Surgical Blood Loss Volume) - A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding
ClinicalTrials.gov ID: NCT00888940
Acronym / sponsor ID: CONSERV-2 / ECAL-CCPB-08-07
Conditions: Bloodloss, Surgical Procedures, Operative
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 243 participants (actual)
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
Study start: Jun 2009
Primary completion: Dec 2009 (actual)
Study completion: Jan 2010 (actual)
First posted: 28 Apr 2009 (estimated)
Results: Posted 17 Jan 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A Phase 2 Randomized Double-Blind Active-Controlled Study in Subjects Exposed to Cardio-pulmonary Bypass During Cardiac Surgery at High Risk of Bleeding

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
ecallantide	Experimental	Drug: Ecallantide
Cyklokapron(R)	Active comparator	Drug: Cyklokapron(R)

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Written informed consent (by study subject) prior to any study-related procedure not part of normal medical care;
Male or female between the ages of 18 and 85 years old, inclusive; and
Planned cardiac surgery using cardio-pulmonary bypass, for one of the following procedures: any repeat sternotomy; surgery to repair or replace more than one valve; combined CABG plus repair or replacement of at least one valve
If female, subject is non-lactating, and is either:Not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;Of childbearing potential but is not pregnant as confirmed by negative pregnancy test at time of screening (based on the β-subunit of HCG), and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.

Key exclusion criteria (30 listed)

Planned primary CABG, single valve repair or replacement surgery, or any off pump procedure;
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;

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
Ecallantide2.25 mg/L pump prime, 0.13 mg/kg loading dose, 2.25 mg/L constant infusion	Drug	ecallantide
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	Drug	Cyklokapron(R)

Primary outcome

Cumulative Volume of Packed Red Blood Cells Transfused
Time frame: 12 hours after the end of surgery

1 secondary outcome

Treatment-emergent Adverse Events.
Time frame: Over the duration of the study.

Results and safety

Results posted to the registry on 17 Jan 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ecallantide	120	92
Cyklokapron(R)	122	101

Primary outcome: Cumulative Volume of Packed Red Blood Cells Transfused

Time frame: 12 hours after the end of surgery. Mean (Standard Deviation). Unit: mL

Measure	Ecallantide n = 106	Cyklokapron(R) n = 109
Value	1223.2 (1334.57)	623.5 (974.64)

Ecallantide vs Cyklokapron(R): p = 0.001, Wilcoxon (Mann-Whitney)

Population analysed: 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

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ecallantide	45 of 109 (41.3%)	93 of 109 (85.3%)	Not reported
Cyklokapron	28 of 109 (25.7%)	91 of 109 (83.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 21724197Bokesch PM, Szabo G, Wojdyga R, Grocott HP, Smith PK, Mazer CD, Vetticaden S, Wheeler A, Levy JH. A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial). J Thorac Cardiovasc Surg. 2012 May;143(5):1022-9. doi: 10.1016/j.jtcvs.2011.06.001. Epub 2011 Jul 2.

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.

Alistair Wheeler, MD, MFPM study director

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

34 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 4 inclusion and 30 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: finished, as of the sponsor's last update on 10 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Germany, Poland, 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. 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 17 Jan 2011). 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 Volume of Packed Red Blood Cells Transfused (time frame: 12 hours after the end of surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00888940, which also lists 1 linked publication.

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 10 Aug 2015.