A Phase 3 interventional study of rThrombin in Spinal Surgery and Vascular Surgery, sponsored by ZymoGenetics. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-01-13.
Sponsored by ZymoGenetics · Phase 3, Interventional, and Treatment
The purpose of this study is to evaluate the safety and immune system response to recombinant thrombin when used to control bleeding in spinal and vascular surgery.
This is a Phase 3b, open-label, single-group, multisite safety and immunogenicity study of recombinant thrombin (rThrombin) in participants who are at least 18 years of age and undergoing spinal or vascular surgery. Eligible participants will receive topical rThrombin during surgery and complete a 1-month follow-up visit.
ZymoGenetics is the lead sponsor of 10 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
rThrombin
Biological: rThrombin
1000 U/mL applied directly or in combination with absorbable gelatin sponge or powder
Number of Participants With Anti-recombinant Thrombin (rThrombin) Product Antibodies at Day 29 in Participants With and Without Anti-bovine Thrombin Product Antibodies at Baseline
Seropositive=with specific anti-bovine thrombin product antibodies; seronegative=without specific anti-bovine thrombin product antibodies.
Time frame: At Day 29
Number of Participants With Death as Outcome, Serious Adverse Events, Treatment-related Adverse Events (AEs), and Treatment-emergent AEs
AE=a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. SAE=an unfavorable medical event that results in death, persistent or significant incapacity, or drug dependency or abuse; is life-threatening, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to study drug. Treatment-emergent=onset on or after treatment start. Grade (Gr) 1=mild, Gr 2=moderate, Gr 3=severe, Gr 4=life threatening/disabling, Gr 5=death.
Time frame: Day 1 (surgery) to Day 29 (end of study), continuously
Number of Participants With Abnormal Hematology Laboratory Results of Common Terminology Criteria (CTC) Grade 2 or Higher at Baseline and Day 29
Hemoglobin, low (g/L): Grade 2=\<100 Grade 3=\<80; Grade 4=\<65. Platelets, low: Grade 2=\<75\*10\^9/L; Grade 3=\<50\*10\^9/L; Grade 4=\<25\*10\^9/L. Leukocytes, low: Grade 2=\<3.0-2.0\*10\^9/L; Grade 3=\<2.0-1.0\*10\^9/L; Grade 4=\<1.0\*10\^9/L. Lymphocytes, low: Grade 2=\<0.8\*10\^9/L; Grade 3=\<0.5\*10\^9/L; Grade 4=\<0.2\*10\^9/L. Neutrophils, low: Grade 2=\<1.5\*10\^9/L; Grade 3=\<1.0\*10\^9/L; Grade 4=\<0.5\*10\^9/L. Changes in hematocrit values observed were not graded for severity.
Time frame: Baseline and Day 29 (end of study)
Number of Participants With Elevations in Coagulation Parameters of CTC Grade 3 or Higher at Baseline and Day 29
Activated partial thromboplastin time (aPTT) elevations: Grade 3=\>2\*upper limit of normal (ULN). International normalized ratio(INR)elevations: Grade 3=\>2\*ULN. Changes in prothrombin time were not graded for toxicity. n=Number of participants with assessments available at that visit.
Time frame: Baseline and Day 29 (end of study)
Number of Participants With Abnormal Laboratory Results in Median Levels of Immunoglobulin A, G, and M at Baseline or Day 29
Abnormal laboratory findings were recorded as AEs when the investigator considered them to be clinically significant (eg, an unusual result for the surgical population or for an individual participant) or when they were associated with symptoms or required treatment or a change in patient management.
Time frame: Baseline and Day 29 (end of study)
Number of Participants With Clinically Significant Changes in Mean Values for Vital Signs (Temperature, Systolic Blood Pressure, Diastolic Blood Pressure, Respiration Rate, Heart Rate) at Baseline and Day 29
Laboratory findings considered clinically significant by investigator when associated with symptoms, required specific treatment, or required a change in participant management. Clinically significant changes in vital signs were reported as adverse events.
Time frame: Baseline and Day 29 (end of study)
| Milestone | rThrombin, 1000 IU/mL |
|---|---|
| Started | 209 |
| Completed | 206 |
| Not completed | 3 |
| Withdrew: Death | 2 |
| Withdrew: Withdrawal by subject | 1 |
Seropositive=with specific anti-bovine thrombin product antibodies; seronegative=without specific anti-bovine thrombin product antibodies.
| Participants | rThrombin, 1000 IU/mL |
|---|---|
| Seropositive at baseline (n=31) | 0 |
| Seronegative at baseline (n=169) | 0 |
| Total (all participants) | 0 |
AE=a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. SAE=an unfavorable medical event that results in death, persistent or significant incapacity, or drug dependency or abuse; is life-threatening, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to study drug. Treatment-emergent=onset on or after treatment start. Grade (Gr) 1=mild, Gr 2=moderate, Gr 3=severe, Gr 4=life threatening/disabling, Gr 5=death.
| Participants | rThrombin, 1000 IU/mL |
|---|---|
| Deaths | 2 |
| Serious adverse events | 47 |
| Treatment-related adverse events (AEs) | 4 |
| Treatment-emergent AEs ≥ Grade 3 | 76 |
| AEs leading to discontinuation | 0 |
Hemoglobin, low (g/L): Grade 2=\<100 Grade 3=\<80; Grade 4=\<65. Platelets, low: Grade 2=\<75\*10\^9/L; Grade 3=\<50\*10\^9/L; Grade 4=\<25\*10\^9/L. Leukocytes, low: Grade 2=\<3.0-2.0\*10\^9/L; Grade 3=\<2.0-1.0\*10\^9/L; Grade 4=\<1.0\*10\^9/L. Lymphocytes, low: Grade 2=\<0.8\*10\^9/L; Grade 3=\<0.5\*10\^9/L; Grade 4=\<0.2\*10\^9/L. Neutrophils, low: Grade 2=\<1.5\*10\^9/L; Grade 3=\<1.0\*10\^9/L; Grade 4=\<0.5\*10\^9/L. Changes in hematocrit values observed were not graded for severity.
| Participants | rThrombin, 1000 IU/mL |
|---|---|
| Hemoglobin, low: Baseline, Grade 2 (n=199) | 13 |
| Hemoglobin, low: Day 29, Grade 2 (n=196) | 12 |
| Hemoglobin, low: Baseline, Grade 3 (n=199) | 3 |
| Hemoglobin, low: Day 29, Grade 3 (n=196) | 0 |
| Hemoglobin, low: Baseline, Grade 4 (n=199) | 0 |
| Hemoglobin, low: Day 29, Grade 4 (n=196) | 0 |
| Platelets, low: Baseline Grade 2 (n=196) | 0 |
| Platelets, low: Day 29, Grade 2 (n=194) | 1 |
| Platelets, low: Baseline, Grade 3 (n=196) | 1 |
| Platelets, low: Day 29, Grade 3 (n=194) | 0 |
| Platelets, low: Baseline, Grade 4 (n=196) | 0 |
| Platelets, low: Day 29, Grade 4 (n=194) | 0 |
| Leukocytes, low: Baseline, Grade 2 (n=199) | 1 |
| Leukocytes, low: Day 29, Grade 2 (n=196) | 0 |
| Leukocytes, low: Baseline, Grade 3 (n=199) | 0 |
| Leukocytes, low: Day 29, Grade 3 (n=196) | 0 |
| Leukocytes, low: Baseline, Grade 4 (n=199) | 0 |
| Leukocytes, low: Day 29, Grade 4 (n=196) | 0 |
| Lymphocytes, low: Baseline, Grade 2 (n=199) | 6 |
| Lymphocytes, low: Day 29, Grade 2 (n=196) | 6 |
| Lymphocytes, low: Baseline, Grade 3 (n=199) | 0 |
| Lymphocytes, low: Day 29, Grade 3 (n=196) | 2 |
| Lymphocytes, low: Baseline, Grade 4 (n=199) | 0 |
| Lymphocytes, low: Day 29, Grade 4 (n=196) | 0 |
| Neutrophils, low: Baseline, Grade 2 (n=199) | 1 |
| Neutrophils, low: Day 29, Grade 2 (n=196) | 1 |
| Neutrophils, low: Baseline, Grade 3 (n=199) | 1 |
| Neutrophils, low: Day 29, Grade 3 (n=196) | 0 |
| Neutrophils, low: Baseline, Grade 4 (n=199) | 0 |
| Neutrophils, low: Day 29, Grade 4 (n=196) | 0 |
Activated partial thromboplastin time (aPTT) elevations: Grade 3=\>2\*upper limit of normal (ULN). International normalized ratio(INR)elevations: Grade 3=\>2\*ULN. Changes in prothrombin time were not graded for toxicity. n=Number of participants with assessments available at that visit.
| Participants | rThrombin, 1000 IU/mL |
|---|---|
| aPTT: Baseline, Grade 3 (n=197) | 6 |
| aPTT: Day 29: Grade 3 (n=199) | 7 |
| INR: Baseline, Grade 3 (n=197) | 1 |
| INR: Day 29: Grade 3 (n=198) | 1 |
Abnormal laboratory findings were recorded as AEs when the investigator considered them to be clinically significant (eg, an unusual result for the surgical population or for an individual participant) or when they were associated with symptoms or required treatment or a change in patient management.
| Participants | rThrombin, 1000 IU/mL |
|---|---|
| Number of Participants With Abnormal Laboratory Results in Median Levels of Immunoglobulin A, G, and M at Baseline or Day 29 | 0 |
Laboratory findings considered clinically significant by investigator when associated with symptoms, required specific treatment, or required a change in participant management. Clinically significant changes in vital signs were reported as adverse events.
| Participants | rThrombin, 1000 IU/mL |
|---|---|
| Number of Participants With Clinically Significant Changes in Mean Values for Vital Signs (Temperature, Systolic Blood Pressure, Diastolic Blood Pressure, Respiration Rate, Heart Rate) at Baseline and Day 29 | 0 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| rThrombin, 1000 IU/mL | — | 47/209 (22.5%) | 197/209 (94.3%) |
| Event | rThrombin, 1000 IU/mL |
|---|---|
| Atrial fibrillationCardiac disorders | 3/209 |
| Deep vein thrombosisVascular disorders | 3/209 |
| HyperkaleamiaMetabolism and nutrition disorders | 3/209 |
| Myocardial infarctionCardiac disorders | 3/209 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 3/209 |
| Wound secretionInjury, poisoning and procedural complications | 3/209 |
| Cardiac failure congestiveCardiac disorders | 2/209 |
| HematomaVascular disorders | 2/209 |
| NauseaGastrointestinal disorders | 2/209 |
| Postoperative wound infectionInfections and infestations | 2/209 |
| Event | rThrombin, 1000 IU/mL |
|---|---|
| Incision site painInjury, poisoning and procedural complications | 94/209 |
| Procedural painInjury, poisoning and procedural complications | 82/209 |
| NauseaGastrointestinal disorders | 56/209 |
| ConstipationGastrointestinal disorders | 42/209 |
| AnemiaBlood and lymphatic system disorders | 35/209 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 26/209 |
| HypotensionVascular disorders | 23/209 |
| PyrexiaGeneral disorders | 20/209 |
| VomitingGastrointestinal disorders | 19/209 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 17/209 |
| Age, Customized(Years) | rThrombin |
|---|---|
| Overall (All status) | 64 (30 to 89) |
| Sex: Female, Male(Participants) | rThrombin |
|---|---|
| Female | 99 |
| Male | 110 |
| Race/Ethnicity, Customized(participants) | rThrombin |
|---|---|
| Hispanic | 25 |
| Asian | 2 |
| Black or African American | 22 |
| White | 160 |
This study is completed, as verified in Jan 2012. You cannot join it, but the record below documents what was studied.
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