The ZEro PLASma Trial (ZEPLAST): Avoidance of Fresh Frozen Plasma in Cardiac Surgery

NCT01471730 | Completed Phase 3

• 2 other identifiers: 7-020-MR2011-005223-40
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, randomized, double blind trial. The rationale of the study is the concept that fresh frozen plasma (FFP) is still largely used in cardiac surgery, despite the fact that prothrombin complexes and fibrinogen are available.The experimental hypothesis is that cardiac surgery patients may be operated with no use of FFP and with a coagulation factors replacement based on fibrinogen and prothrombin complexes (when needed). Primary endpoint: Transfusion avoidance Secondary endpoints: Transfusion limitation, massive blood transfusion, bleeding. Study population: high-risk adult cardiac surgery patients Sample size : 2 groups of 60 patients each

Conditions

Heart Disease

Keywords

Transfusions; Fresh Frozen Plasma; Fibrinogen; Prothrombin complex

Outcome Measures

Primary Outcomes (1)

• Avoidance of allogeneic blood products transfusion

  Includes avoidance of packed red cells, FFP, platelet concentrates, cryoprecipitates

  30 days

Secondary Outcomes (3)

• Reduction in allogeneic blood products transfusions

  30 days

• Massive blood transfusion

  First postoperative 24 hours

• Bleeding

  First postoperative 12 hours

Study Arms (3)

Saline solution

PLACEBO COMPARATOR

Drug: Saline solution

Fibrinogen

ACTIVE COMPARATOR

Drug: Fibrinogen

Prothrombin complex

ACTIVE COMPARATOR

Drug: Prothrombin complex

Interventions

Fibrinogen DRUG

All the patients randomized and not withdrawn will be tested 20 minutes before removal of aortic cross clamping with a Thromboelastometric fibrinogen test FIBTEM (Rotem) . They will all receive either human fibrinogen concentrate (according to the formula: (22 \[mm\] - MCF \[mm\]) \* body weight \[kg\] / 140 \[m\] = whole g fibrinogen to be dosed as HFC) (treatment group) or placebo (control group). Study drug or placebo has to be administered after protamine.

Also known as: RIASTAP

Fibrinogen

Saline solution DRUG

Normal saline will be administered to control patients.

Also known as: Placebo

Saline solution

Prothrombin complex DRUG

After 15min from study drug administration and in presence of ongoing microvascular bleeding, we run a CT EXTEM. In case of prolonged CT time at EXTEM as long as 80 seconds \[M1\] , they will receive coagulation factors concentrates (Confidex) at a weight-based dose of 7 U/kg b.w. (treatment group) or placebo.

Also known as: CONFIDEX

Prothrombin complex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients will be screened according to a modified TRUST1 Transfusion Score. This score attributes 1 point to each of the following conditions:
• Hb level \< 13.5 g/dL
• Weight \< 77 kg
• Female sex
• Age \> 65 years
• Non elective surgery
• Serum creatinine \> 1.36 mg/dL
• Redo operation
• Non isolated surgery
• Age \> 65 years
• Non elective surgery
• Combined cardiac operation with expected CPB duration \> 90 minutes
• At least one additional risk factor within the following: Age \> 65 years; Non elective surgery; Serum creatinine \> 1.36 mg/dL; Redo operation

You may not qualify if:

• Age \< 18 years
• Patients under thienopyridines
• Known coagulopathy
• Known autoimmune disorders
• Participation in another RCT
• Pregnancy
• Emergency operation
• Baseline HCT \< 35%
• Baseline Antithrombin \< 80%
• BSA \< 1.7 m2
• WITHDRAWAL CRITERION:
• Lowest HCT on CPB \< 23%
• Transfusions during CPB
• Patients randomized and not withdrawn will be DOSED with the investigational drugs.

Sponsors & Collaborators

• IRCCS Policlinico S. Donato: lead
• CSL Behring: collaborator

Study Sites (1)

IRCCS Policlinico San Donato

San Donato Milanese, MI, 20097, Italy

Location

Related Publications (7)

• Rahe-Meyer N, Pichlmaier M, Haverich A, Solomon C, Winterhalter M, Piepenbrock S, Tanaka KA. Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study. Br J Anaesth. 2009 Jun;102(6):785-92. doi: 10.1093/bja/aep089. Epub 2009 May 2.

  PMID: 19411671 BACKGROUND

• Solomon C, Pichlmaier U, Schoechl H, Hagl C, Raymondos K, Scheinichen D, Koppert W, Rahe-Meyer N. Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth. 2010 May;104(5):555-62. doi: 10.1093/bja/aeq058. Epub 2010 Mar 26.

  PMID: 20348140 BACKGROUND

• Stanworth SJ, Brunskill SJ, Hyde CJ, McClelland DB, Murphy MF. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol. 2004 Jul;126(1):139-52. doi: 10.1111/j.1365-2141.2004.04973.x.

  PMID: 15198745 BACKGROUND

• Alghamdi AA, Davis A, Brister S, Corey P, Logan A. Development and validation of Transfusion Risk Understanding Scoring Tool (TRUST) to stratify cardiac surgery patients according to their blood transfusion needs. Transfusion. 2006 Jul;46(7):1120-9. doi: 10.1111/j.1537-2995.2006.00860.x.

  PMID: 16836558 BACKGROUND

• Rahe-Meyer N, Solomon C, Winterhalter M, Piepenbrock S, Tanaka K, Haverich A, Pichlmaier M. Thromboelastometry-guided administration of fibrinogen concentrate for the treatment of excessive intraoperative bleeding in thoracoabdominal aortic aneurysm surgery. J Thorac Cardiovasc Surg. 2009 Sep;138(3):694-702. doi: 10.1016/j.jtcvs.2008.11.065. Epub 2009 May 17.

  PMID: 19698858 BACKGROUND

• Bolliger D, Szlam F, Molinaro RJ, Rahe-Meyer N, Levy JH, Tanaka KA. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth. 2009 Jun;102(6):793-9. doi: 10.1093/bja/aep098. Epub 2009 May 6.

  PMID: 19420005 BACKGROUND

• Ranucci M, Baryshnikova E, Crapelli GB, Rahe-Meyer N, Menicanti L, Frigiola A; Surgical Clinical Outcome REsearch (SCORE) Group. Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery. J Am Heart Assoc. 2015 Jun 2;4(6):e002066. doi: 10.1161/JAHA.115.002066.

  PMID: 26037084 DERIVED

MeSH Terms

Conditions

Heart Diseases

Interventions

Fibrinogen; Saline Solution; prothrombin complex concentrates

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Marco Ranucci, MD

  IRCCS Policlinico S. Donato

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Research in the Department of the Anesthesia and Intensive care

Study Record Dates

• First Submitted: November 7, 2011
• First Posted: November 16, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 31, 2015

Record last verified: 2015-03

Locations

IT (1)