Trial Outcomes & Findings for Human Fibrinogen Concentrate in Pediatric Cardiac Surgery (NCT NCT02822599)

NCT ID: NCT02822599

Last Updated: 2021-09-16

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: Within 24 hours of surgery
• Results posted on: 2021-09-16

Participant Flow

Participant milestones

Measure	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. RiaStAP: To decrease post-operative bleeding volume.	Saline Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Overall Study STARTED	15	15
Overall Study COMPLETED	15	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Human Fibrinogen Concentrate in Pediatric Cardiac Surgery

Baseline characteristics by cohort

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Race · Mixed Race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black/African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Postoperative Blood Loss After Surgery (Estimated Blood Loss (EBL))	35 cc/kg Interval 21.0 to 61.0	33 cc/kg Interval 26.0 to 48.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 2 hr Hemoglobin (Hg) mg/dL Measure	13.6 mg/dL Interval 11.0 to 15.2	12.5 mg/dL Interval 11.7 to 13.3

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 24-hr Hemoglobin (Hg) mg/dL	13.8 mg/dL Interval 11.7 to 15.8	12.4 mg/dL Interval 11.0 to 14.7

PRIMARY outcome

Timeframe: 2 hour

Post-operative 2 hr Hematocrit (HCT) between the treatment and placebo group.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 2 hr Hematocrit (HCT) Measure	40.9 percent of hematocrit Interval 32.7 to 43.5	35.9 percent of hematocrit Interval 35.4 to 38.8

PRIMARY outcome

Timeframe: 24 hour

Post-operative 24 hr Hematocrit (HCT) between the treatment and placebo group

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 24 hr Hematocrit (HCT) Measure	38.9 percent Interval 34.1 to 45.3	35.4 percent Interval 32.9 to 42.8

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 2 hr Platelets Count Test (PLT) 10K/uL	282.0 10x10^3 platelets/uL Interval 234.0 to 309.0	224.0 10x10^3 platelets/uL Interval 192.0 to 311.0

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 24 hr Platelets Count Test (PLT) 10K/uL	249.0 10x10^3 platelets/uL Interval 197.0 to 297.0	247.0 10x10^3 platelets/uL Interval 189.0 to 300.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 2 hr Prothrombin (PT) Seconds	17.0 seconds Interval 16.7 to 18.5	16.5 seconds Interval 15.8 to 17.2

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 24 hr Prothrombin (PT) Seconds	16.0 seconds Interval 15.4 to 18.2	16.1 seconds Interval 14.9 to 17.1

PRIMARY outcome

Timeframe: 2 hour

Post-operative 2 hr International Normalize Ratio (INR) between the treatment and placebo group

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 2 hr International Normalize Ratio (INR)	1.4 ratio Interval 1.3 to 1.5	1.4 ratio Interval 1.2 to 1.4

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 24 hr International Normalize Ratio (INR)	1.3 ratio Interval 1.2 to 1.5	1.3 ratio Interval 1.2 to 1.4

PRIMARY outcome

Timeframe: 2 hour

Post-operative 2 hr Partial Thromboplastin Time (PTT) between the treatment and placebo group

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 2 hr Partial Thromboplastin Time (PTT) Seconds	36.7 seconds Interval 33.7 to 41.1	35.2 seconds Interval 32.1 to 36.6

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 24 hr Partial Thromboplastin Time (PTT) Seconds	35.5 seconds Interval 34.1 to 38.6	31.5 seconds Interval 30.3 to 35.5

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 2 hr Fibrinogen mg/dL	258.0 mg/dL Interval 238.0 to 338.0	330.0 mg/dL Interval 281.0 to 385.0

PRIMARY outcome

Timeframe: 24 hour

Post-operative 24 hr Fibrinogen between the treatment and placebo group

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative 24 hr Fibrinogen mg/dL	416.5 mg/dL Interval 318.5 to 512.0	403.0 mg/dL Interval 324.0 to 465.0

SECONDARY outcome

Timeframe: 24 hours after surgery

Patients who suffered from respiratory failure post operatively.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-Operative Respiratory Failure Adverse Events	3 participants	3 participants

SECONDARY outcome

Timeframe: within 24 hours of surgery

Patient who suffered from Thrombus events post-operatively.

Outcome measures

Measure	RiaSTAP n=15 Participants Group 1 will receive an infusion of RiaSTAP after termination of CPB at a dose of 70 mg/kg after randomization to this group. RiaStAP: To decrease post-operative bleeding volume.	Saline n=15 Participants Group 2 will receive a placebo consisting of Normal Saline 0.9% (NS) after randomization to this group. Saline: Placebo consisting of normal saline 0.9%
Post-operative Thrombus Adverse Events	4 participants	2 participants

Adverse Events

RiaStap

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	RiaStap n=15 participants at risk RiaStap\_Treatment received an infusion of RiaSTAP, right after the termination of CPB at a dose of 70 mg/kg.	Placebo n=15 participants at risk Placebo\_Treatment received a placebo of Normal Saline 0.9% (NS) during the same time period. The volume of NS was calculated to be the same volume that would be used IF the patient were receiving RiaSTAP.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	20.0% 3/15 • Number of events 3 • 24 hours after surgery; There were no other adverse events measured	20.0% 3/15 • Number of events 3 • 24 hours after surgery; There were no other adverse events measured
Cardiac disorders Thrombus	26.7% 4/15 • Number of events 4 • 24 hours after surgery; There were no other adverse events measured	13.3% 2/15 • Number of events 2 • 24 hours after surgery; There were no other adverse events measured

Other adverse events

Adverse event data not reported

Additional Information

Jenny Esteves

Nicklaus Children's Hospital

Phone: 786-624-2854

Email: jenny.esteves@nicklaushealth.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place