Human Fibrinogen Concentrate in Pediatric Cardiac Surgery (RiaSTAP)

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ClinicalTrials.gov Identifier: NCT02822599

Recruitment Status : Completed

First Posted : July 4, 2016

Results First Posted : September 16, 2021

Last Update Posted : September 16, 2021

Sponsor:

Information provided by (Responsible Party):

Christopher Tirotta, MD, MBA, Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Study Description

Brief Summary:

Condition or disease	Intervention/treatment	Phase
Hypofibrinogenemia Afibrinogenemia Bleeding Disorders	Drug: RiaStAP Drug: Saline	Phase 4

Detailed Description:

The goal of the study is to determine whether the use of Human Fibrinogen Concentrate (RiaSTAP) will decrease blood loss and the need for component blood therapy in neonates and infants undergoing cardiopulmonary bypass. RiaSTAP will be administered after termination of Cardiopulmonary Bypass (CPB) at a dose of 70 mg/kg, in a prospective, randomized, controlled study. We hypothesize that the administration of RiaSTAP in this manner will reduce peri-operative bleeding and transfusion requirements.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	30 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	The Role of Human Fibrinogen Concentrate (RiaSTAP) in Decreasing Blood Loss and the Need for Component Blood Therapy in Infants Undergoing Cardiopulmonary Bypass.
Actual Study Start Date :	June 1, 2017
Actual Primary Completion Date :	August 26, 2019
Actual Study Completion Date :	December 24, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Congenital afibrinogenemia

MedlinePlus related topics: Bleeding

Drug Information available for: Sodium chloride Fibrinogen

Genetic and Rare Diseases Information Center resources: Afibrinogenemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: RiaSTAP Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group.	Drug: RiaStAP To decrease post-operative bleeding volume. Other Name: Fibrinogen Concentrate Human
Placebo Comparator: Saline Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group.	Drug: Saline Placebo consisting of normal saline 0.9% Other Name: Normal Saline 0.9%

Outcome Measures

Primary Outcome Measures :

Postoperative Blood Loss After Surgery (Estimated Blood Loss (EBL)) [ Time Frame: Within 24 hours of surgery ]
Primary outcome efficacy: Estimated blood loss (EBL); median; A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Thereafter, as per routine care, ROTEM analysis was performed at least every 30 minutes while in the OR, or sooner, at the discretion of the OR team. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algorithm.
Post-operative 2 hr Hemoglobin (Hg) mg/dL Measure [ Time Frame: 2 hour ]
Post-operative 2 hr hemoglobin (Hg) between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Thereafter, as per routine care, ROTEM analysis was performed at least every 30 minutes while in the OR, or sooner, at the discretion of the OR team. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algorithm.
Post-operative 24-hr Hemoglobin (Hg) mg/dL [ Time Frame: 24 hr ]
Post-operative 24-hr hemoglobin (Hg) between treatment and placebo. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Thereafter, as per routine care, ROTEM analysis was performed at least every 30 minutes while in the OR, or sooner, at the discretion of the OR team. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algorithm.
Post-operative 2 hr Hematocrit (HCT) Measure [ Time Frame: 2 hour ]
Post-operative 2 hr Hematocrit (HCT) between the treatment and placebo group.
Post-operative 24 hr Hematocrit (HCT) Measure [ Time Frame: 24 hour ]
Post-operative 24 hr Hematocrit (HCT) between the treatment and placebo group
Post-operative 2 hr Platelets Count Test (PLT) 10K/uL [ Time Frame: 2 hour ]
Post-operative 2 hr Platelets Count Test (PLT) between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algor
Post-operative 24 hr Platelets Count Test (PLT) 10K/uL [ Time Frame: 24 hour ]
Post-operative 24 hr Platelets Count Test (PLT) between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algo
Post-operative 2 hr Prothrombin (PT) Seconds [ Time Frame: 2 hour ]
Post-operative 2 hr Prothrombin (PT) between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Thereafter, as per routine care, ROTEM analysis was performed at least every 30 minutes while in the OR, or sooner, at the discretion of the OR team. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algorithm.
Post-operative 24 hr Prothrombin (PT) Seconds [ Time Frame: 24 hour ]
Post-operative 24 hr Prothrombin (PT) between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Thereafter, as per routine care, ROTEM analysis was performed at least every 30 minutes while in the OR, or sooner, at the discretion of the OR team. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algorithm.
Post-operative 2 hr International Normalize Ratio (INR) [ Time Frame: 2 hour ]
Post-operative 2 hr International Normalize Ratio (INR) between the treatment and placebo group
Post-operative 24 hr International Normalize Ratio (INR) [ Time Frame: 24 hour ]
Post-operative 24 hr International Normalize Ratio (INR) between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM ana
Post-operative 2 hr Partial Thromboplastin Time (PTT) Seconds [ Time Frame: 2 hour ]
Post-operative 2 hr Partial Thromboplastin Time (PTT) between the treatment and placebo group
Post-operative 24 hr Partial Thromboplastin Time (PTT) Seconds [ Time Frame: 24 hour ]
Post-operative 24 hr Partial Thromboplastin Time (PTT) between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analys
Post-operative 2 hr Fibrinogen mg/dL [ Time Frame: 2 hour ]
Post-operative 2 hr Fibrinogen between the treatment and placebo group. A transfusion algorithm was developed based on three previous studies, modified for pediatrics. Clinically significant bleeding requiring treatment was defined as a rate >10 cc kg-1 hr-1 calculated every 15 minutes while in the OR, measured by blood in the suction canister. In cases of continued bleeding following randomization to HFC or placebo, cryoprecipitate was considered for fibrinogen <200 mg/dL or FIBTEM MCF <7 mm. Thereafter, as per routine care, ROTEM analysis was performed at least every 30 minutes while in the OR, or sooner, at the discretion of the OR team. Once the patient left the OR, ROTEM was performed at least every 60 minutes for the first 6 hours or until clinically significant bleeding had stopped. Blood products transfused after CPB separation were based on a pre-defined protocol. Recommended volumes of each therapy were based on pre-defined formulae and a ROTEM analysis algorithm.
Post-operative 24 hr Fibrinogen mg/dL [ Time Frame: 24 hour ]
Post-operative 24 hr Fibrinogen between the treatment and placebo group

Secondary Outcome Measures :

Post-Operative Respiratory Failure Adverse Events [ Time Frame: 24 hours after surgery ]
Patients who suffered from respiratory failure post operatively.
Post-operative Thrombus Adverse Events [ Time Frame: within 24 hours of surgery ]
Patient who suffered from Thrombus events post-operatively.

Eligibility Criteria

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Ages Eligible for Study:	up to 1 Year (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Neonatal and infant cardiac patients presenting for open-heart surgery at Nicklaus Children's Hospital will be eligible for enrollment in the study.

Exclusion Criteria:

Patients who fall outside of the age range for the study will be excluded. Patients known to have had an anaphylactic or severe reaction to the drug or its components will not be enrolled. At the time of the rewarming ROTEM, any patient with a FIBTEM MCF > 15mm, will be excluded.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02822599

Locations

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United States, Florida
Nickalus Children's Hospital f/k/a Miami Children's Hospital
Miami, Florida, United States, 33155
Nicklaus Children's Hospital
Miami, Florida, United States, 33155

Sponsors and Collaborators

Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Investigators

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Principal Investigator:	Christopher Tirotta, MD	Director Cardiac Anesthesia

Study Documents (Full-Text)

Documents provided by Christopher Tirotta, MD, MBA, Nicklaus Children's Hospital f/k/a Miami Children's Hospital:

Study Protocol and Statistical Analysis Plan [PDF] December 7, 2017

More Information

Additional Information:

Nicklaus Children's Hospital This link exits the ClinicalTrials.gov site

Publications:

Dacey LJ, Munoz JJ, Baribeau YR, Johnson ER, Lahey SJ, Leavitt BJ, Quinn RD, Nugent WC, Birkmeyer JD, O'Connor GT. Reexploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group. Arch Surg. 1998 Apr;133(4):442-7.

Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Reexploration for bleeding is a risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg. 1996 May;111(5):1037-46.

Paparella D, Brister SJ, Buchanan MR. Coagulation disorders of cardiopulmonary bypass: a review. Intensive Care Med. 2004 Oct;30(10):1873-81. Epub 2004 Jul 24. Review.

Miller BE, Tosone SR, Guzzetta NA, Miller JL, Brosius KK. Fibrinogen in children undergoing cardiac surgery: is it effective? Anesth Analg. 2004 Nov;99(5):1341-1346. doi: 10.1213/01.ANE.0000134811.27812.F0.

Kern FH, Morana NJ, Sears JJ, Hickey PR. Coagulation defects in neonates during cardiopulmonary bypass. Ann Thorac Surg. 1992 Sep;54(3):541-6.

Chan AK, Leaker M, Burrows FA, Williams WG, Gruenwald CE, Whyte L, Adams M, Brooker LA, Adams H, Mitchell L, Andrew M. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost. 1997 Feb;77(2):270-7. Erratum in: Thromb Haemost 1997 May;77(5):1047.

Karlsson M, Ternström L, Hyllner M, Baghaei F, Nilsson S, Jeppsson A. Plasma fibrinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery: a prospective observational study. Transfusion. 2008 Oct;48(10):2152-8. doi: 10.1111/j.1537-2995.2008.01827.x. Epub 2008 Jul 24.

Karlsson M, Ternström L, Hyllner M, Baghaei F, Flinck A, Skrtic S, Jeppsson A. Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. A prospective randomised pilot study. Thromb Haemost. 2009 Jul;102(1):137-44. doi: 10.1160/TH08-09-0587.

Rahe-Meyer N, Pichlmaier M, Haverich A, Solomon C, Winterhalter M, Piepenbrock S, Tanaka KA. Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study. Br J Anaesth. 2009 Jun;102(6):785-92. doi: 10.1093/bja/aep089. Epub 2009 May 2.

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Responsible Party:	Christopher Tirotta, MD, MBA, Director Cardiac Anesthesia, Nicklaus Children's Hospital f/k/a Miami Children's Hospital
ClinicalTrials.gov Identifier:	NCT02822599
Other Study ID Numbers:	NCH0000201496
First Posted:	July 4, 2016 Key Record Dates
Results First Posted:	September 16, 2021
Last Update Posted:	September 16, 2021
Last Verified:	June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Christopher Tirotta, MD, MBA, Nicklaus Children's Hospital f/k/a Miami Children's Hospital:


CBP, congenital heart defects, cardiopulmonary bypass

Additional relevant MeSH terms:

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Hemostatic Disorders Blood Coagulation Disorders Afibrinogenemia Hematologic Diseases Vascular Diseases	Cardiovascular Diseases Hemorrhagic Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Genetic Diseases, Inborn

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