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

Congenital Heart Disease Clinical Trial

— ZEPLAST-PED  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04434001
• Other study ID #: ZEPLAST-PED
• Status: Terminated
• Phase: Phase 2
• Start date: February 27, 2020
• Est. completion date: June 30, 2021

Study information

• Verified date: October 2021
• Source: IRCCS Policlinico S. Donato
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: June 30, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Bleeding
• Cardiac Defect
• Congenital Heart Disease
• Fibrinogenopenia; Acquired
• Heart Defects, Congenital
• Heart Diseases
• Hemorrhage
• Lung Injury
• Surgery--Complications
• Transfusion Reaction
• Transfusion-Associated Circulatory Overload
• Transfusion-Related Acute Lung Injury

Intervention

Drug:
• Fibrinogen Concentrate Human
Treatment of acquired postoperatively fibrinogen deficiency as assessed by ROTEM FIBTEM test.
• Prothrombin Complex Concentrate
Treatment of acquired postoperatively thrombin generation deficiency as assessed by ROTEM EXTEM test.

Biological:
• Fresh Frozen Plasma
Treatment of acquired postoperative coagulopathy as assessed by ROTEM FIBTEM and INTEM tests.

Locations

Country	Name	City	State
Italy	IRCCS Policlinico San Donato	San Donato Milanese	MI

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Donato

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Bianchi P, Cotza M, Beccaris C, Silvetti S, Isgrò G, Pomè 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. — View Citation

Moore SB. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis. Crit Care Med. 2006 May;34(5 Suppl):S114-7. Review. — View Citation

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. — View Citation

Ranucci M, Bianchi P, Cotza M, Beccaris C, Silvetti S, Isgrò 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transfusion of Fresh Frozen Plasma (FFP)	Number of patients transfused with FFP	First 48 hours after surgery
Secondary	Postoperative bleeding	Amount of blood collected by chest drainages	First 12, 24 and 48 hours after surgery
Secondary	Severe bleeding	Number of patients who experienced severe bleeding (higher than 30 ml/kg in the first 12 hours after surgery)	First 12 hours after surgery
Secondary	Surgical re-exploration for bleeding	Number of patients requiring surgical re-exploration due to bleeding (bleeding with no coagulopathies detected or refractory to pharmacological treatment)	First 12, 24 and 48 hours after surgery