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

Phase 2

Terminated

• Conditions: Bleeding; Cardiac Defect; Surgery--Complications; Fibrinogenopenia; Acquired; Transfusion-Related Acute Lung Injury; Transfusion-Associated Circulatory Overload; Congenital Heart Disease
• Interventions: Biological: Fresh Frozen Plasma; Drug: Fibrinogen Concentrate Human; Drug: Prothrombin Complex Concentrate

• Registration Number: NCT04434001
• Lead Sponsor: IRCCS Policlinico S. Donato

Brief Summary

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

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.

Study Timeline

• Study Start: 2020-02-27
• Study First Submitted: 2020-06-12
• Study First Submitted QC: 2020-06-12
• Study First Posted: 2020-06-16
• Primary Completion: 2021-05-31
• Study Completion: 2021-06-30
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-28
• Last Update Posted: 2021-11-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Fresh Frozen Plasma	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.
ZEPLAST	Fibrinogen Concentrate Human	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.
ZEPLAST	Prothrombin Complex Concentrate	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.

Primary Outcome Measures

Name	Time	Method
Transfusion of Fresh Frozen Plasma (FFP)	First 48 hours after surgery	Number of patients transfused with FFP

Secondary Outcome Measures

Name	Time	Method
Postoperative bleeding	First 12, 24 and 48 hours after surgery	Amount of blood collected by chest drainages
Surgical re-exploration for bleeding	First 12, 24 and 48 hours after surgery	Number of patients requiring surgical re-exploration due to bleeding (bleeding with no coagulopathies detected or refractory to pharmacological treatment)
Severe bleeding	First 12 hours after surgery	Number of patients who experienced severe bleeding (higher than 30 ml/kg in the first 12 hours after surgery)

Trial Locations

Locations (1)

IRCCS Policlinico San Donato; 🇮🇹 San Donato Milanese, MI, Italy