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

NCT04434001 | Terminated Phase 2 DMC

• 1 other identifier: ZEPLAST-PED
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Transfusion of Fresh Frozen Plasma (FFP)

  Number of patients transfused with FFP

  First 48 hours after surgery

Secondary Outcomes (3)

• Postoperative bleeding

  First 12, 24 and 48 hours after surgery

• Severe bleeding

  First 12 hours after surgery

• Surgical re-exploration for bleeding

  First 12, 24 and 48 hours after surgery

Study Arms (2)

ZEPLAST

EXPERIMENTAL

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; Drug: Prothrombin Complex Concentrate

Control

ACTIVE COMPARATOR

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

Interventions

Fibrinogen Concentrate Human DRUG

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

Also known as: Haemocomplettan

ZEPLAST

Prothrombin Complex Concentrate DRUG

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

Also known as: Confidex

ZEPLAST

Fresh Frozen Plasma BIOLOGICAL

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

Control

Eligibility Criteria

• Age: 1 Day - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS Policlinico S. Donato: lead

Study Sites (1)

IRCCS Policlinico San Donato

San Donato Milanese, MI, 20097, Italy

Location

Related Publications (5)

• 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.

  PMID: 16617254 BACKGROUND

• 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.

  PMID: 26893405 BACKGROUND

• 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.

  PMID: 28510741 BACKGROUND

• 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.

  PMID: 31250738 BACKGROUND

• 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.

  PMID: 36408876 DERIVED

MeSH Terms

Conditions

Hemorrhage; Afibrinogenemia; Transfusion-Related Acute Lung Injury; Transfusion Reaction; Heart Defects, Congenital; Hemophilia B

Interventions

Fibrinogen; Factor IX

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Acute Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Immune System Diseases; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors; Enzyme Precursors; Enzymes and Coenzymes

Study Officials

• Marco Ranucci, MD

  IRCCS Policlinico S. Donato

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Cardiothoracic and Vascular Anesthesia and Intensive Care

Study Record Dates

• First Submitted: June 12, 2020
• First Posted: June 16, 2020
• Study Start: February 27, 2020
• Primary Completion: May 31, 2021
• Study Completion: June 30, 2021
• Last Updated: November 3, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)