Fibrinogen Concentrate In Children Cardiac Surgery 2 (FiCCS2)

Profilatic Fibrinogen Concentrate Reduces Postoperative Bleeding in Pediatric Cardiac Surgery With Cardiopulmonary Bypass: Randomized Study

The purporse of this study is evaluate whether fibrinogen concentrate reduces postoperative bleeding in pediatric cardiac surgery with cardiopulmonary by-pass.

Study Overview

• Status: Unknown
• Conditions: Blood Coagulation Disorders; C.Surgical Procedure; Cardiac; Hypofibrinogenemia
• Intervention / Treatment: Drug: Fibrinogen Concentrate; Other: control

Detailed Description

Cardiac surgery in children may be associated with excessive perioperative bleeding. Perioperative excessive bleeding is associated with need of transfusion with allogeneic blood products such as red blood cells, fresh frozen plasma, platelet pools, and cryoprecipitate. Furthermore, bleeding may result in re-exploration, which is associated with increased morbidity and mortality.Recent studies have shown that patients and children undergoing cardiac surgery with pump often experience a significant drop in their levels and function of fibrinogen, and it would be in part responsible for the bleeding. Fibrinogen concentrate (Haemocomplettan P)may reduce perioperative bleeding, requirements of blood transfusion and clinical outcomes in children undergoing cardiac surgery with pump.

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403000
    • Recruiting
    • Incor - Heart Institute - University of Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 10 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cardiac surgery with pump
• Written informed consent
• Age under 28 days of life or RACHS-1 equal or greater than 3 or reoperation with age under 10 years

Exclusion Criteria:

• Coagulopathy (INR > 1.5)
• Low platelet count (lower than 100.000)
• Product or albumin allergy
• Active endocarditis
• Blalock-Taussig
• Heart transplant
• Anemia (hemoglobin < 10 g/dL)
• Impossibility to receive blood transfusion
• Hepatic dysfunction (total bilirubin > 1.5 mg/dL)
• Known or suspected hypersensitivity to fibrinogen concentrate
• Thrombophilia or previous thrombosis
• Participation in another study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: fibrinogen concentrate; patients randomized to fibrinogen group receive intravenous infusion of drug prepared based on ROTEM measurement of maximum clot firmness (MCF)	Drug: Fibrinogen Concentrate; Fibrinogen Concentrate is to be administered as an intravenous infusion after discontinuation of cardiopulmonary bypass and administration of protamine. Subjects are to be given Fibrinogen Concentrate at an individually determined dose based on FIBTEM MCF and body weight as follows: (15 [mm] - MCF [mm]) * body weight [kg] / 140 [mm*kg/g] = gram fibrinogen to be dosed as Fibrinogen Concentrate. Fibrinogen Concentrate is to be infused over 1 to 2 minutes. After Fibrinogen Concentrate infusion, bleeding treatment will follow the predefined, standardized treatment regimen.
PLACEBO_COMPARATOR: control; patients randomized to the control group will receive the infusion of 0.9% saline (SF0,9%) prepared based on ROTEM measurement of maximum clot firmness (MCF)	Other: control; 0.9% saline is to be administered as an intravenous infusion after discontinuation of cardiopulmonary bypass and administration of protamine. Patients randomized to the control group will receive the infusion of 0.9% saline (SF0,9%) prepared based on ROTEM measurement of maximum clot firmness (MCF). 0.9% saline is to be infused over 1 to 2 minutes. After 0.9% saline infusion, bleeding treatment will follow the predefined, standardized treatment regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of postoperative bleeding	The amount of blood loss (tube drainage) in the first 6 hours of ICU admission and daily until the seventh day of ICU. Re-exploration is mandatory if the patient presente excessive bleeding not responsive to clinical measures (warming, coagulopathy correction and/or thrombocytopenia correction), associated hemodynamic instability or evidence of cardiac tamponade.	Within 7 days after cardiac surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount and type of blood transfusion	The amount and type of intraoperative blood transfusion within the first 6 hours of ICU admission and daily up to the seventh day of ICU.	within 7 days after cardiac surgery
Rate of acute kidney injury	According to pediatric RIFLE, will be measured daily.	within 28 days after cardiac surgery
Rate of cardiac complications	Occurrence of arrhythmias, low cardiac output, cardiogenic shock and the need of postoperative ventricular assistance	within 28 days after cardiac surgery
Rate of neurological complications	Incidence of stroke	within 28 days after cardiac surgery
Rate of infection complications	Infection (surgical wound infection, pneumonia, urinary tract infection and bloodstream infection), sepsis, severe sepsis and septic shock.	within 28 days after cardiac surgery
Correlation between clot firmness (FIBTEM) and plasma fibrinogen	Relationship among the results of FIBTEM-A10 and plasma fibrinogen level will be performed at the same time	After the cardiopulmonary bypass (CPB) weaning and after drug administration during the surgery.
Evaluation of the clot firmness before and after the intervention	Evaluation between FIBTEM-A10 that will be measured after the cardiopulmonary bypass (CPB) weaning and after drug intervention	After the cardiopulmonary bypass (CPB) weaning and after drug administration during the surgery.
Evaluation of plasma fibrinogen before and after the intervention	Evaluation between the fibrinogen level that will be measured after the cardiopulmonary bypass (CPB) weaning, after drug intervention and in the ICU admission.	After the cardiopulmonary bypass (CPB) weaning, after drug administration during the surgery and in ICU admission.
Duration of mechanical ventilation	number of hours in which the patient reiman intubated between the date of surgery and discharge from the ICU	within 28 days after cardiac surgery
Length of vasoactive drugs	number of hours in which the patient will use vasoactive drugs between the date of surgery and discharge from the ICU	within 28 days after cardiac surgery
Length of ICU stay	number of days between the admission and discharge from the ICU.	within 28 days after cardiac surgery
Length of hospital stay	number of days between the date of surgery and hospital discharge.	within 28 days after cardiac surgery
Rate of mortality	Death from all causes occurring up to 28 days after surgery.	within 28 days after cardiac surgery

Collaborators and Investigators

• Sponsor: Filomena R B G Galas
• Investigators: Principal Investigator: Filomena RG Galas, University of São Paulo

Publications and helpful links

General Publications

• Galas FR, de Almeida JP, Fukushima JT, Vincent JL, Osawa EA, Zeferino S, Camara L, Guimaraes VA, Jatene MB, Hajjar LA. Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery: a randomized pilot trial. J Thorac Cardiovasc Surg. 2014 Oct;148(4):1647-55. doi: 10.1016/j.jtcvs.2014.04.029. Epub 2014 Apr 18.

Helpful Links

• Bleeding, Bleeding Disorders, Heart Surgery

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2019
• Primary Completion (ANTICIPATED): June 1, 2019
• Study Completion (ANTICIPATED): June 1, 2019

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (ACTUAL): March 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 21, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Bleeding; Fibrinogen; Cardiac surgical procedures
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders
• Other Study ID Numbers: 3864.12.120

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No