Clinical trial NCT04434001: ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery
Official title: ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery Randomized Controlled Pilot Phase II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: IRCCS Policlinico S. Donato
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Transfusion of Fresh Frozen Plasma (FFP)
timeFrame: First 48 hours after surgery
Secondary outcomes:
measure: Postoperative bleeding
timeFrame: First 12, 24 and 48 hours after surgery
measure: Severe bleeding
timeFrame: First 12 hours after surgery
measure: Surgical re-exploration for bleeding
timeFrame: First 12, 24 and 48 hours after surgery
Other outcomes:
Locations:
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
state: MI
Study officials:
affiliation: IRCCS Policlinico S. Donato
name: Marco Ranucci, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
citation: 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.
citation: 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.