Blood Loss, Surgical
Conditions
Brief summary
The objective of this study is to assess the immunogenicity and safety of recombinant Thrombin (rThrombin) in patients with prior rThrombin exposure.
Detailed description
The safety, immunogenicity, and efficacy of rThrombin have been evaluated in Phase 2 and Phase 3 studies in the following surgical indications: spinal surgery, major hepatic resection, peripheral arterial bypass (PAB) surgery, arteriovenous (AV) graft formation for hemodialysis access, and skin graft surgery following burn injury. Limited data on rThrombin reexposure currently exist. This study will assess the immunogenicity and safety of rThrombin in participants who are undergoing a surgical procedure during which topical rThrombin application is planned and who previously received rThrombin in Phase 3 clinical trials or during prior spine, AV graft formation, or PAB surgical procedures.
Interventions
BIOLOGICALrThrombin, 1000 IU/mL
At least 1 application of reconstituted rThrombin, 1000 IU/mL, applied topically directly to the bleeding site, per product labeling.
Sponsors
ZymoGenetics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previous enrollment in a ZymoGenetics-sponsored Phase 3 study and the recipient of treatment with rThrombin in that study or the recipient of commercially-available rThrombin in a prior spine, arteriovenous graft formation, or peripheral artery bypass surgical procedure * Age of 18 years or older at time of consent * Bleeding indicating treatment with rThrombin during the course of the surgical procedure * Signed informed consent document approved by an institutional review board or independent ethics committee
Exclusion criteria
* Currently undergoing a procedure requiring cardiopulmonary bypass or involving the aortic arch * Known hypersensitivity to rThrombin product or any of its components * Currently undergoing a surgical procedure where the use of other thrombin-containing hemostatic agents is planned * Medical, social, or psychosocial factors that, in the opinion of the investigator, could affect the participant's safety or compliance with study procedures * Treatment with any experimental agent within 30 days of study enrollment or treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number or Participants With Antirecombinant Thrombin (rThrombin) Product Antibody at Baseline and Day 29 | At baseline and Day 29 | Immunogenicity of rThrombin product was evaluated using an enzyme-linked immunosorbent assay for detection of antirThrombin product antibody and a neutralizing antibody assay to characterize the potential of antibodies to rThrombin product to neutralize the activity of human plasma-derived thrombin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | Baseline through Day 29, continuously | An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment. |
| Number of Participants With AEs by Maximum Severity | Baseline to Day 29, continuously | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AE severity was assessed using Common Terminology Criteria for Adverse Events, Version 13.0: Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=fatal. |
Countries
United States
Participant flow
Pre-assignment details
Of 31 participants enrolled, all received treatment with recombinant thrombin (rThrombin).
Participants by arm
| Arm | Count |
|---|---|
| rThrombin, 1000 IU/mL At least 1 application of reconstituted rThrombin, 1000 IU/mL, applied topically directly to the bleeding site. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | rThrombin, 1000 IU/mL |
|---|---|
| Age, Customized Median | 61.0 Years |
| Age, Customized | 59.5 Years STANDARD_DEVIATION 12.3 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 19 Participants |
| Type of surgery Arterial reconstruction/peripheral arterial bypass | 4 Participants |
| Type of surgery Arteriovenous vascular access procedure | 3 Participants |
| Type of surgery Other | 1 Participants |
| Type of surgery Spinal | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 31 |
| serious Total, serious adverse events | 6 / 31 |
Outcome results
Primary
Number or Participants With Antirecombinant Thrombin (rThrombin) Product Antibody at Baseline and Day 29
Immunogenicity of rThrombin product was evaluated using an enzyme-linked immunosorbent assay for detection of antirThrombin product antibody and a neutralizing antibody assay to characterize the potential of antibodies to rThrombin product to neutralize the activity of human plasma-derived thrombin.
Time frame: At baseline and Day 29
Population: Participants who received treatment with rThrombin and had data available from both baseline and Day 29 antibody assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rThrombin, 1000 IU/mL | Number or Participants With Antirecombinant Thrombin (rThrombin) Product Antibody at Baseline and Day 29 | Baseline | 0 Participants |
| rThrombin, 1000 IU/mL | Number or Participants With Antirecombinant Thrombin (rThrombin) Product Antibody at Baseline and Day 29 | Day 29 | 0 Participants |
Secondary
Number of Participants With AEs by Maximum Severity
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AE severity was assessed using Common Terminology Criteria for Adverse Events, Version 13.0: Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=fatal.
Time frame: Baseline to Day 29, continuously
Population: All participants who received treatment with rThrombin.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rThrombin, 1000 IU/mL | Number of Participants With AEs by Maximum Severity | Mild | 1 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With AEs by Maximum Severity | Moderate | 18 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With AEs by Maximum Severity | Severe | 9 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With AEs by Maximum Severity | Life-threatening | 0 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With AEs by Maximum Severity | Fatal | 1 Participants |
Secondary
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation
An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time frame: Baseline through Day 29, continuously
Population: All participants who received treatment with rThrombin.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rThrombin, 1000 IU/mL | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | Death | 1 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | SAEs | 6 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | Treatment-related SAEs | 0 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | AEs | 29 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | Treatment-related AEs | 0 Participants |
| rThrombin, 1000 IU/mL | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs), Treatment-related Adverse Events, and AEs Leading to Discontinuation | AEs leading to discontinuation | 0 Participants |