Platelet Transfusion During Neonatal Open Heart Surgery

NCT03045068 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HSC-MS-16-1034
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: Dilutional thrombocytopenia after cardiopulmonary bypass (CPB) is universal and administration of donor apheresis platelets just prior to termination of bypass will assist in early correction of coagulopathy, early hemostasis and lesser donor exposure of blood products after cardiac surgery. Background: What is the Problem? - Bleeding, Transfusion and Outcomes

1. 1.Excessive bleeding after neonatal cardiac surgery has been independently associated with increased adverse events, morbidity and mortality.1,2 Bleeding after neonatal open-heart surgery has multiple etiologies such as immaturity of the building blocks of coagulation, effects of deep hypothermia, longer CPB times, altered flow states and dilutional state induced by being on CPB leading to low platelet count, low platelet function, low fibrinogen levels, altered fibrinogen polymerization, complement activation, etc.2,3 The strongest predictor of transfusion after cardiopulmonary bypass in children was deemed to be the CPB circuit volume and the effect of hemodilution.4
2. 2.The dilutional coagulopathy after neonatal CPB requires intense damage control resuscitation with massive transfusion of platelets, packed red blood cells (PRBC), cryoprecipitate, fresh frozen plasma (FFP) and supplemental factor concentrates. In a previous study at this institution (IRB# HSC-MS-13-0647), we have shown that in neonates undergoing open-heart surgery there was a significant drop in platelet counts after bypass (71% change, baseline= 268 ± 90, Post CPB= 76 ± 27, 109/L). Associated with this drop , the average intraoperative transfusion load in neonates undergoing cardiac surgery with CPB at our institution constitutes of PRBC= 63± 43 ml/kg, FFP=51± 21 ml/kg, cryoprecipitate =12+6 ml/kg, platelets = 28 +16 ml/kg and cell-saver =27± 10 ml/kg. In addition 72% of these patients were exposed to a 3-factor prothrombin complex concentrate (Bebulin®). Although this "throw the kitchen sink" approach is effective in achieving hemostasis, it comes with significant effects on post CPB hemodynamics, constantly changing hematocrit, variable blood volume with inability to achieve steady state inotropic state affecting cardiac output, oxygen delivery and adding to pulmonary hypertension.

Conditions

Cardiac Disease; Cardiac Surgery; Cardiopulmonary Bypass; Platelet Transfusion; Arrythmia, Cardiac; Mortality

Outcome Measures

Primary Outcomes (1)

• Amount of Blood Products Transfused

  All Blood products administered (PRBC, FFP, Cryo, Platelets) from termination of CPB to first 24 hours post op

  0-72 hours

Secondary Outcomes (8)

• Number of Exposures of 4-PCC and Factor 7

  0-72 hours

• Time From End of CPB to Sternal Closure (Chest Approximation)

  0-72 hours

• Chest Tube Output

  0-24 hours

• Inotropic Support at the Time of Entry to the Pediatric Intensive Care Unit (PICU) as Indicated by Inotrope Score

  At the time of entry to the pediatric intensive care unit (PICU)

• Length of Mechanical Ventilation

  from start of mechanical ventilation to end of mechanical ventilation (about 4-8 days)

Study Arms (2)

Study Group

EXPERIMENTAL

Platelet Transfusion Management 1. Pre-Termination of CPB- Platelet Transfusion 10ml/kg to be administered to the patient via central venous access when the patient has been rewarmed to 35\*C, (the Sano or BT shunt clip is still on in children with SV physiology) 2. Post CPB- Platelet transfusion 10ml/kg via a central venous line is continued at a rate of 100 ml/hour till completion.

Biological: Platelet Transfusion; Biological: FFP and Cryoprecipitate; Biological: PRBC and cell saver Transfusion; Biological: Factor Concentrate (Bebulin)

Control Group

ACTIVE COMPARATOR

Platelet Transfusion Management 1. Pre-Termination of CPB- No intervention 2. Post CPB- Platelet transfusion 20ml/kg via a central venous line is continued at a rate of 100 ml/hour till completion.

Biological: Platelet Transfusion; Biological: FFP and Cryoprecipitate; Biological: PRBC and cell saver Transfusion; Biological: Factor Concentrate (Bebulin)

Interventions

Platelet Transfusion BIOLOGICAL

Post CPB- Platelet transfusion 20ml/kg via a central venous line is continued at a rate of 100 ml/hour till completion. 1. Initial transfusion to occur proximal to the hemofilter on the MUF circuit for as long as MUF lasts 2. Subsequent platelet transfusion continued till completion via central venous access to the patient

Also known as: Platelet

Control Group; Study Group

FFP and Cryoprecipitate BIOLOGICAL

1. 1 unit of cryoprecipitate administered during MUF and or after MUF as needed 2. FFP transfusion 10ml/kg during MUF and or after MUF as needed

Also known as: FFP

Control Group; Study Group

PRBC and cell saver Transfusion BIOLOGICAL

1\. Transfuse for target Hematocrit \> 40 in neonates with SV physiology; Transfuse for Hematocrit\> 33 for 2-Ventricle physiology

Also known as: PRBC

Control Group; Study Group

Factor Concentrate (Bebulin) BIOLOGICAL

1\. Based on clinical bleeding and achievement of hemostasis

Also known as: Bebulin

Control Group; Study Group

Eligibility Criteria

• Age: 1 Day - 3 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All neonates and infants less than 3 months of age under 4 kilograms undergoing open heart surgery and cardiopulmonary bypass

You may not qualify if:

• Redo open heart surgery
• Bleeding Disorders - such as von Willebrand Disease, Hemophilia

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Heart Diseases; Arrhythmias, Cardiac

Interventions

Platelet Transfusion; Platelet Count; Factor IX

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics; Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Platelet Function Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Nischal K Gautam, MD
• Organization: The University of Texas Health Science Center at Houston

Nischal.K.Gautam@uth.tmc.edu

713-500-6200

Study Officials

• Nischal K Gautam, MD

  The University of Texas Health Science at Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Model Details: Prospective Randomized trial in neonates comparing platelet apheresis transfusion prior to termination of CPB versus standard transfusion of platelet apheresis after modified ultrafiltration and protamine administration

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: February 7, 2017
• Study Start: April 11, 2017
• Primary Completion: October 1, 2018
• Study Completion: November 1, 2018
• Last Updated: March 8, 2023
• Results First Posted: March 8, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)