ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery

NCT ID: NCT04434001

Last Updated: 2021-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-27

Study Completion Date

2021-06-30

Brief Summary

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In pediatric patients (newborns and infants weighing less than 10 kg) undergoing cardiac surgery with extracorporeal circulation postoperative bleeding represents a known complication with a significant impact on outcome. Fresh frozen plasma (FFP) for bleeding management is associated, particularly in this kind of patients, to volume overload and a significative increase of Transfusion Related Acute Lung Injury (TRALI), further worsening the postoperative outcome. In the adult patient FFP employment could be almost completely canceled by administration of concentrated hemostatic components - the fibrinogen concentrate and prothrombin complex concentrate (PCC). We designed this phase II pilot study to establish whether an analogous strategy, modified accordingly to pediatric physiology, could be safely and successfully applied in newborns and infants.

Detailed Description

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The study population will be randomized to two groups: ZEPLAST and control, respectively.

The two groups will receive the same priming solution (containing Red Blood Cells and albumin 5%) and heparin/protamine management. In both groups coagulation will be assessed with rotational thromboelastometry (ROTEM - EXTEM, INTEM, HEPTEM and FIBTEM tests) after heparin antagonization. In case of bleeding, coagulopathies will be treated differently:

* in the ZEPLAST group, fibrinogen deficiency (FIBTEM Maximum Clot Firmness MCF \< 8 mm) will be treated with 30 mg/kg of concentrated fibrinogen; low thrombin generation (EXTEM Clotting Time CT \> 100 s) will be treated with 20 mg/kg of prothrombin complex concentrate;
* in the control group, coagulopathies will be treated with 10-20 ml/kg of FFP. In case of refractory bleeding, PCC and fibrinogen can be administered as a rescue treatment.

Further ROTEM tests will be performed at 24 and 48 hours post surgery. Outcome parameters will be collected at the same timepoints.

Conditions

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Bleeding Cardiac Defect Surgery--Complications Fibrinogenopenia; Acquired Transfusion-Related Acute Lung Injury Transfusion-Associated Circulatory Overload Congenital Heart Disease

Keywords

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bleeding pediatric cardiac surgery fresh frozen plasma fibrinogen concentrate prothrombin complex concentrate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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ZEPLAST

In case of bleeding and:

* CT INTEM \> CT HEPTEM by 25% : give protamine 0.25 mg/kg;
* MCF FIBTEM \< 8 mm : give Fibrinogen Concentrate 30 mg/kg;
* CT EXTEM \> 100 s : give Prothrombin Complex Concentrate 20 mg/kg.

Group Type EXPERIMENTAL

Fibrinogen Concentrate Human

Intervention Type DRUG

Treatment of acquired postoperatively fibrinogen deficiency as assessed by ROTEM FIBTEM test.

Prothrombin Complex Concentrate

Intervention Type DRUG

Treatment of acquired postoperatively thrombin generation deficiency as assessed by ROTEM EXTEM test.

Control

In case of bleeding and:

* CT INTEM \> CT HEPTEM by 25% : give protamine 0.25 mg/kg;
* fibrinogen and/or thrombin generation deficiency : give FFP 10-20 ml/kg.

Group Type ACTIVE_COMPARATOR

Fresh Frozen Plasma

Intervention Type BIOLOGICAL

Treatment of acquired postoperative coagulopathy as assessed by ROTEM FIBTEM and INTEM tests.

Interventions

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Fibrinogen Concentrate Human

Treatment of acquired postoperatively fibrinogen deficiency as assessed by ROTEM FIBTEM test.

Intervention Type DRUG

Prothrombin Complex Concentrate

Treatment of acquired postoperatively thrombin generation deficiency as assessed by ROTEM EXTEM test.

Intervention Type DRUG

Fresh Frozen Plasma

Treatment of acquired postoperative coagulopathy as assessed by ROTEM FIBTEM and INTEM tests.

Intervention Type BIOLOGICAL

Other Intervention Names

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Haemocomplettan Confidex

Eligibility Criteria

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Inclusion Criteria

* newborns and infants with weight lower than 10 kg undergoing cardiac surgery with extracorporeal circulation:
* informed consent signed by both parents or legal guardian.

Exclusion Criteria

* emergency surgery;
* known congenital coagulopathy or suspected based on anamnesis;
* participation to other clinical trials;
* known hypersensitivity to components and excipients of FFP , prothrombin complex concentrate or fibrinogen concentrate.
Minimum Eligible Age

1 Day

Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IRCCS Policlinico S. Donato

OTHER

Sponsor Role lead

Responsible Party

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Marco Ranucci

Head of Cardiothoracic and Vascular Anesthesia and Intensive Care

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marco Ranucci, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Policlinico S. Donato

Locations

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IRCCS Policlinico San Donato

San Donato Milanese, MI, Italy

Site Status

Countries

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Italy

References

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Moore SB. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis. Crit Care Med. 2006 May;34(5 Suppl):S114-7. doi: 10.1097/01.CCM.0000214312.20718.3E.

Reference Type BACKGROUND
PMID: 16617254 (View on PubMed)

Ranucci M, Baryshnikova E. Fibrinogen supplementation after cardiac surgery: insights from the Zero-Plasma trial (ZEPLAST). Br J Anaesth. 2016 May;116(5):618-23. doi: 10.1093/bja/aev539. Epub 2016 Feb 17.

Reference Type BACKGROUND
PMID: 26893405 (View on PubMed)

Bianchi P, Cotza M, Beccaris C, Silvetti S, Isgro G, Pome G, Giamberti A, Ranucci M; Surgical and Clinical Outcome REsearch (SCORE) group. Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial. Br J Anaesth. 2017 May 1;118(5):788-796. doi: 10.1093/bja/aex069.

Reference Type BACKGROUND
PMID: 28510741 (View on PubMed)

Ranucci M, Bianchi P, Cotza M, Beccaris C, Silvetti S, Isgro G, Giamberti A, Baryshnikova E. Fibrinogen levels and postoperative chest drain blood loss in low-weight (<10 kg) children undergoing cardiac surgery. Perfusion. 2019 Nov;34(8):629-636. doi: 10.1177/0267659119854246. Epub 2019 Jun 28.

Reference Type BACKGROUND
PMID: 31250738 (View on PubMed)

Hayes K, Fernando MC, Jordan V. Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding. Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2.

Reference Type DERIVED
PMID: 36408876 (View on PubMed)

Other Identifiers

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ZEPLAST-PED

Identifier Type: -

Identifier Source: org_study_id