Ovarian Cancer
Conditions
Keywords
Tumor of ovary, Surgical blood loss, Postoperative blood loss, Preventive therapy, Thromboembolism
Brief summary
The purpose of the study is to determine if a standardized single dose tranexamic acid given intravenously immediately preoperatively reduces the perioperative bleeding volume and reduces the need of blood transfusion in women undergoing surgery for advanced ovarian cancer.
Interventions
0.9% NaCl solution; 0.15 ml/kg body weight added to 100 ml 0.9% NaCl solution. The volume is given intravenously immediate before skin incision at surgery.
DRUGTranexamic acid
Tranexamic acid, 100 mg/ml; 15 mg/kg body weight added to 100 ml 0.9% NaCl solution given as a single dose intravenously immediately prior to skin incision at surgery
Sponsors
Preben Kjolhede, MD, professor
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females ages 18 or older with a pelvic or abdominal tumor suspected or histopathologically proven ovarian cancer FIGO stage II-IV who are undergoing primary surgery with the intention of performing optimal cytoreductive radical surgery. * Understand and speak Swedish * Accept participation in the study after written and verbal information and sign informed consent.
Exclusion criteria
* Allergy to tranexamic acid * Having had tranexamic acid within the recent 30 days * Previous or present episode of thromboembolic events . * Previous or present treatment within the recent 3 months with anticoagulant. * Previous or present known coagulopathy * Myocardial infarction within the previous 12 months or instable angina pectoris which, according to the investigator, may increase the risk for complications significantly in case of a lowering of the hemoglobin. * Significant renal failure with serum-creatinine \> 250 µmol/l. * Severe psychiatric dysfunction or mentally substantially disabled.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Perioperative Bleeding Volume | From start of operation to discharge from hospital, up to 5 weeks | Estimation of total blood loss was based on the estimation of the Hb balance method (Brecher, et al.1997) with the assumption that the body blood volume was normalised on the fifth postoperative day. The haemoglobin level was assessed preoperatively and on the fifth postoperative day. The predicted blood volume (PBV, l) was calculated according to the method described by Nadler et al. (1962), using body weight and height. The extravasation of haemoglobin was calculated taking into account allogenic transfused haemoglobin. Total blood loss perioperatively was related to the patient's preoperative haemoglobin value. Blood loss due to haematomas or a reoperation within the first five days after surgery was also considered. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Receiving Blood Transfusions | From start of operation to discharge from hospital, up to 5 weeks | Total number of RBC-transfused women in each group |
| Number of Units of Red Blood Cells (RBC) Transfused | From start of operation to discharge from hospital, up to 5 weeks | Total number of red blood cells (RBC) transfused across all participants |
| Median Number of Transfused Units of Red Blood Cells (RBC) | From start of operation to discharge from hospital, up to 5 weeks | Median number of red blood cells transfused among those who received RBC transfusions |
| Number of Patients With Clinically or Radiologically Verified Thromboembolic Events Within 5 Weeks Postoperatively | From time of operation to 5 weeks postoperatively. | Thromboembolic events including arterial thrombosis, muscle vein thrombosis, superficial and deep venous thrombosis. |
Countries
Sweden
Participant flow
Recruitment details
Between March 2008 and May 2012 one hundred women with presumed advanced ovarian cancer scheduled for radical debulking surgery att one of two university hospitals or two central hospitals in the southeast health region of Sweden and who complied with inclusion/exclusion criteria were asked to participate in the study.
Pre-assignment details
No significant events occured after participant enrollment prior to assignment to a group.
Participants by arm
| Arm | Count |
|---|---|
| Tranexamic Group Tranexamic acid
Tranexamic acid: Tranexamic acid, 100 mg/ml; 15 mg/kg body weight added to 100 ml 0.9% NaCl solution given as a single dose intravenously immediately prior to scin incision at surgery | 50 |
| Placebo Group 0.9% NaCl solution
0.9% NaCl solution: 0.9% NaCl solution; 0.15 ml/kg body weight added to 100 ml 0.9% NaCl solution. The volume is given intravenously immediate before scin incision at surgery. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Group | Total | Tranexamic Group |
|---|---|---|---|
| Age, Continuous | 64.5 years | 63 years | 63 years |
| Age, Customized 60-69 years of age | 17 participants | 41 participants | 24 participants |
| Age, Customized <60 years of age | 15 participants | 30 participants | 15 participants |
| Age, Customized >=70 years of age | 18 participants | 29 participants | 11 participants |
| Arterial hypertension/vascular disease | 13 participants | 35 participants | 22 participants |
| Body mass index Normal weight (BMI<25) | 31 participants | 50 participants | 19 participants |
| Body mass index Obese (BMI >=30) | 5 participants | 11 participants | 6 participants |
| Body mass index Overweight (BMI 25-29) | 14 participants | 39 participants | 25 participants |
| Body mass index | 24 kg/m^2 | 25.1 kg/m^2 | 25.9 kg/m^2 |
| Cardiac disease | 1 participants | 6 participants | 5 participants |
| Diabetes mellitus | 7 participants | 10 participants | 3 participants |
| Height | 1.63 meter | 1.64 meter | 1.67 meter |
| Low-dose aspirin medication | 5 participants | 12 participants | 7 participants |
| Parity | 2 births | 2 births | 2 births |
| Predicted Blood Volume (PBV) | 3.87 liter | 3.99 liter | 4.16 liter |
| Previous hysterectomy | 3 participants | 9 participants | 6 participants |
| Previous laparotomy | 21 participants | 46 participants | 25 participants |
| RBC transfusion preoperatively | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Sweden | 50 participants | 100 participants | 50 participants |
| Sex/Gender, Customized Female | 50 Participants | 100 Participants | 50 Participants |
| Smokers | 5 participants | 13 participants | 8 participants |
| Weight | 64.3 kilogram | 67.6 kilogram | 71 kilogram |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 18 / 50 | 17 / 50 |
| serious Total, serious adverse events | 10 / 50 | 14 / 50 |
Outcome results
Primary
Perioperative Bleeding Volume
Estimation of total blood loss was based on the estimation of the Hb balance method (Brecher, et al.1997) with the assumption that the body blood volume was normalised on the fifth postoperative day. The haemoglobin level was assessed preoperatively and on the fifth postoperative day. The predicted blood volume (PBV, l) was calculated according to the method described by Nadler et al. (1962), using body weight and height. The extravasation of haemoglobin was calculated taking into account allogenic transfused haemoglobin. Total blood loss perioperatively was related to the patient's preoperative haemoglobin value. Blood loss due to haematomas or a reoperation within the first five days after surgery was also considered.
Time frame: From start of operation to discharge from hospital, up to 5 weeks
Population: All patients underwent surgery. A negative value of total blood loss was received when the postoperative haemoglobin level was higher than the preoperative haemoglobin or when a blood transfusion was given, based on the Hb balance method of blood loss calculation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tranexamic Group | Perioperative Bleeding Volume | 520 milliliter |
| Placebo Group | Perioperative Bleeding Volume | 730 milliliter |
p-value: 0.03Wilcoxon (Mann-Whitney)
Secondary
Median Number of Transfused Units of Red Blood Cells (RBC)
Median number of red blood cells transfused among those who received RBC transfusions
Time frame: From start of operation to discharge from hospital, up to 5 weeks
Population: Participants who received RBC transfusions
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tranexamic Group | Median Number of Transfused Units of Red Blood Cells (RBC) | 2 units |
| Placebo Group | Median Number of Transfused Units of Red Blood Cells (RBC) | 2 units |
p-value: 0.46Wilcoxon (Mann-Whitney)
Secondary
Number of Patients Receiving Blood Transfusions
Total number of RBC-transfused women in each group
Time frame: From start of operation to discharge from hospital, up to 5 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Group | Number of Patients Receiving Blood Transfusions | 15 participants |
| Placebo Group | Number of Patients Receiving Blood Transfusions | 22 participants |
p-value: 0.07Wilcoxon (Mann-Whitney)
Secondary
Number of Patients With Clinically or Radiologically Verified Thromboembolic Events Within 5 Weeks Postoperatively
Thromboembolic events including arterial thrombosis, muscle vein thrombosis, superficial and deep venous thrombosis.
Time frame: From time of operation to 5 weeks postoperatively.
Population: Information about postoperative events after discharge retrieved in patient file for the patients with withdrew consent prior to 5-weeks follow-up.~56% of the patients underwent lower extremity duplex ultrasound.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tranexamic Group | Number of Patients With Clinically or Radiologically Verified Thromboembolic Events Within 5 Weeks Postoperatively | 2 Participants |
| Placebo Group | Number of Patients With Clinically or Radiologically Verified Thromboembolic Events Within 5 Weeks Postoperatively | 5 Participants |
p-value: 0.2295% CI: [0.05, 2.72]Fisher Exact
Secondary
Number of Units of Red Blood Cells (RBC) Transfused
Total number of red blood cells (RBC) transfused across all participants
Time frame: From start of operation to discharge from hospital, up to 5 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Group | Number of Units of Red Blood Cells (RBC) Transfused | 38 units |
| Placebo Group | Number of Units of Red Blood Cells (RBC) Transfused | 53 units |
p-value: 0.46Wilcoxon (Mann-Whitney)