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

San Donato Group (GSD)

Status and phase: Terminated; Phase 2

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

Treatments: Biological: Fresh Frozen Plasma; Drug: Fibrinogen Concentrate Human; Drug: Prothrombin Complex Concentrate

Study type: Interventional

Funder types: Other

Identifiers

NCT04434001

ZEPLAST-PED

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 40 patients

Sex: All

Ages: 1 day to 2 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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40 participants in 2 patient groups

ZEPLAST

Experimental group

Description:

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.

Treatment:

Drug: Prothrombin Complex Concentrate

Drug: Fibrinogen Concentrate Human

Control

Active Comparator group

Description:

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.

Treatment:

Biological: Fresh Frozen Plasma