Surgical Bleeding
Conditions
Keywords
surgical hemostasis, bleeding, fibrin sealant, fibrinogen, thrombin, spray dried
Brief summary
The purpose of the study is to determine if Raplixa plus Gelfoam is better than Gelfoam alone in stopping mild to moderate bleeding in children having surgery.
Interventions
DRUGRaplixa
Raplixa is a biological product approved for use in adults to help control bleeding from small blood vessels when standard surgical techniques, such as suture, ligature or cautery, are ineffective or impractical. When applied to a bleeding site, Raplixa is dissolved in the blood and a reaction starts between the fibrinogen and thrombin proteins. This results in the formation of blood clots to help stop the bleeding.
DEVICEGelfoam
Gelfoam Sterile Sponge is a medical device (USP, Pfizer) intended for application to bleeding surfaces as a hemostatic. It is a water-insoluble, off-white, nonelastic, porous, pliable product. It may be cut without fraying, used wet or dry, and is able to absorb many times its weight in blood and other fluids.
DRUGRescue treatment
Thrombin-containing hemostats included in standard care at the site
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
Before Surgery Inclusion Criteria: * Was at least 36 weeks gestational age at birth (if an infant less than 6 months old) and is no older than 17 years at time of treatment * Has a legal representative (parent or guardian) who signed an institutional review board (IRB)-approved informed consent document * If at least 7 years old or appropriate age as defined by local regulations, may be required to sign an IRB-approved assent document * Is scheduled to undergo one of the surgical procedures described in the protocol * If female and of child-bearing potential, subject has negative pregnancy test on the day of surgery (baseline) * If a sexually active male or female of reproductive potential, agrees to use a medically accepted form of contraception from the time of consent to completion of all follow-up study visits During Surgery Inclusion Criteria: * Has mild or moderate bleeding/oozing * Has TBS surface area no more than 100 cm\^2 * Has not received any whole blood, fresh frozen plasma (FFP), cryoprecipitate, or platelets within 24 hours prior to study drug (packed red blood cell (PRBC) transfusions are allowed) * Had no complication during surgery other than bleeding which, in the opinion of the Investigator, may interfere with the assessment of efficacy or safety
Exclusion criteria
* Has any clinically significant laboratory or vital sign value, chronic disease state, or congenital coagulation disorder (eg, hemophilia A or B) that the investigator determines could interfere with the assessment of efficacy or pose a safety risk to the participant * Is unwilling to receive blood products * Has known antibodies or hypersensitivity to porcine gelatine, Raplixa or any of it's components, or other thrombin preparations or coagulation factors * Has medical, social, or psychosocial factors that, in the opinion of the Investigator, could impact safety of the participant or compliance with study procedures, including protocol-defined limits on participating in other clinical studies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Reached Hemostasis at the Target Bleeding Site (TBS) Within 4 Minutes | within 4 minutes | Count of Participants who Reached Hemostasis at the TBS within 4 minutes of the first study drug application |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Reached Hemostasis at the TBS Within 5 Minutes | within 5 minutes | Count of Participants who Reached Hemostasis at the TBS within 5 minutes of the first study drug application |
| Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | within 97 days | Clinically significant changes in safety measures are recorded as adverse events. Participants with TEAEs that are deemed by the principal investigator or the independent data monitoring committee as possibly or definitely treatment-related (including device-related) are included in the count for this secondary outcome measure. |
Countries
United States
Participant flow
Recruitment details
Of 87 planned participants, only 55 were randomized before the trial was terminated early due to device related (non-safety) issues
Participants by arm
| Arm | Count |
|---|---|
| Raplixa Plus Gelfoam Participants treated with Raplixa in addition to Gelfoam | 36 |
| Gelfoam Alone Participants treated only with Gelfoam | 18 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Raplixa Plus Gelfoam | Gelfoam Alone | Total |
|---|---|---|---|
| Age, Continuous | 6.6 years | 9.7 years | 6.9 years |
| Age, Customized Age Cohorts Cohort 1 = 11 to < 18 years | 13 Participants | 9 Participants | 22 Participants |
| Age, Customized Age Cohorts Cohort 2 = 2 to < 11 years | 19 Participants | 9 Participants | 28 Participants |
| Age, Customized Age Cohorts Cohort 3 = 6 months to < 2 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Customized Age Cohorts Cohort 4 = Birth to < 6 months | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 8 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 10 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) White | 26 Participants | 9 Participants | 35 Participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 21 Participants | 9 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 37 | 0 / 18 |
| other Total, other adverse events | 0 / 36 | 0 / 18 |
| serious Total, serious adverse events | 7 / 36 | 1 / 18 |
Outcome results
Primary
Number of Participants Who Reached Hemostasis at the Target Bleeding Site (TBS) Within 4 Minutes
Count of Participants who Reached Hemostasis at the TBS within 4 minutes of the first study drug application
Time frame: within 4 minutes
Population: modified Intent to Treat (mITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raplixa Plus Gelfoam | Number of Participants Who Reached Hemostasis at the Target Bleeding Site (TBS) Within 4 Minutes | 30 Participants |
| Gelfoam Alone | Number of Participants Who Reached Hemostasis at the Target Bleeding Site (TBS) Within 4 Minutes | 5 Participants |
Comparison: Odds Ratio (OR) and Wald-based 95% Confidence intervals (CIs) are from logistic regression model comparing the response between treatment arms.p-value: =0.00195% CI: [4.58, 401]Regression, Logistic
Secondary
Number of Participants Who Reached Hemostasis at the TBS Within 5 Minutes
Count of Participants who Reached Hemostasis at the TBS within 5 minutes of the first study drug application
Time frame: within 5 minutes
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raplixa Plus Gelfoam | Number of Participants Who Reached Hemostasis at the TBS Within 5 Minutes | 33 Participants |
| Gelfoam Alone | Number of Participants Who Reached Hemostasis at the TBS Within 5 Minutes | 7 Participants |
Secondary
Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs)
Clinically significant changes in safety measures are recorded as adverse events. Participants with TEAEs that are deemed by the principal investigator or the independent data monitoring committee as possibly or definitely treatment-related (including device-related) are included in the count for this secondary outcome measure.
Time frame: within 97 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raplixa Plus Gelfoam | Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Gelfoam Alone | Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |