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

Sponsor

IRCCS Policlinico S. Donato (Other)

Overall Status

Terminated

CT.gov ID

NCT04434001

Collaborator

(none)

Enrollment

Location

Arms

16.1

Actual Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bleeding Cardiac Defect Surgery--Complications Fibrinogenopenia; Acquired Transfusion-Related Acute Lung Injury Transfusion-Associated Circulatory Overload Congenital Heart Disease	Drug: Fibrinogen Concentrate Human Drug: Prothrombin Complex Concentrate Biological: Fresh Frozen Plasma	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery Randomized Controlled Pilot Phase II Study

Actual Study Start Date :

Feb 27, 2020

Actual Primary Completion Date :

May 31, 2021

Actual Study Completion Date :

Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Fibrinogen Concentrate Human Treatment of acquired postoperatively fibrinogen deficiency as assessed by ROTEM FIBTEM test. Other Names: Haemocomplettan Drug: Prothrombin Complex Concentrate Treatment of acquired postoperatively thrombin generation deficiency as assessed by ROTEM EXTEM test. Other Names: Confidex
Active Comparator: 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.	Biological: Fresh Frozen Plasma Treatment of acquired postoperative coagulopathy as assessed by ROTEM FIBTEM and INTEM tests.

Arm

Intervention/Treatment

Experimental: 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.

Drug: Fibrinogen Concentrate Human

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

Other Names:

Haemocomplettan

Drug: Prothrombin Complex Concentrate

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

Other Names:

Confidex

Active Comparator: 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.

Biological: Fresh Frozen Plasma

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

Outcome Measures

Primary Outcome Measures

Transfusion of Fresh Frozen Plasma (FFP) [First 48 hours after surgery]
Number of patients transfused with FFP

Secondary Outcome Measures

Postoperative bleeding [First 12, 24 and 48 hours after surgery]
Amount of blood collected by chest drainages
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)
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 2 Years

Sexes Eligible for Study:

All

Accepts 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.