Tranexamic Acid in Surgery of Advanced Ovarian Cancer
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: The Tranexamic acid group The group of women receiving Tranexamic acid intravenously immediately before the surgery |
Drug: 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 skin incision at surgery
Other Names:
|
Placebo Comparator: The placebo group The group of women receiving saline solution (0.9% NaCl) intravenously immediately before the surgery |
Drug: 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 skin incision at surgery.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Dept of Obstetric and Gynecology, Ryhov Central Hospital | Jönköping | Sweden | 55185 | |
2 | Department of Obstetrics and Gynecology, Kalmar Central Hospital | Kalmar | Sweden | 39185 | |
3 | University Hospital, Department of Obsterics and Gynecology, | Linköping | Sweden | 581 85 |
Sponsors and Collaborators
- Preben Kjolhede, MD, professor
Investigators
- Principal Investigator: Ulf Leandersson, MD, Dept. of Obstetrics and Gynecology, Kalmar Central Hospital, 391 85 Kalmar
- Principal Investigator: Laila Falknäs, MD, Dept of Obstetrics and Gynecology, Ryhov Central Hospital, 58185 Jönköping
- Study Chair: Preben Kjölhede, MD,PhD, Department of Obstetrics and Gynecology, University Hospital, Linköping
- Study Chair: Torsten Johansson, MD, PhD, Dept. of Orthopedic Surgery, University Hospital, 58185 Linköping Sweden
- Study Chair: Helena Zachrisson, MD,PhD, Dept of Physiology, University Hospital, 58185 Linköping Sweden
Study Documents (Full-Text)
None provided.More Information
Publications
- Abu-Rustum NR, Richard S, Wilton A, Lev G, Sonoda Y, Hensley ML, Gemignani M, Barakat RR, Chi DS. Transfusion utilization during adnexal or peritoneal cancer surgery: effects on symptomatic venous thromboembolism and survival. Gynecol Oncol. 2005 Nov;99(2):320-6. Epub 2005 Aug 2.
- Brecher ME, Monk T, Goodnough LT. A standardized method for calculating blood loss. Transfusion. 1997 Oct;37(10):1070-4.
- Dolan S, Fitch M. The management of venous thromboembolism in cancer patients. Br J Nurs. 2007 Nov 22-Dec 12;16(21):1308-12. Review.
- Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999 Jun;57(6):1005-32. Review.
- Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by tranexamic acid during and after caesarian section: a multi-center, randomized trial. Eur J Obstet Gynecol Reprod Biol. 2004 Feb 10;112(2):154-7.
- Johansson T, Lisander B, Ivarsson I. Mild hypothermia does not increase blood loss during total hip arthroplasty. Acta Anaesthesiol Scand. 1999 Nov;43(10):1005-10.
- Johansson T, Pettersson LG, Lisander B. Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients. Acta Orthop. 2005 Jun;76(3):314-9.
- Lindoff C, Rybo G, Astedt B. Treatment with tranexamic acid during pregnancy, and the risk of thrombo-embolic complications. Thromb Haemost. 1993 Aug 2;70(2):238-40.
- Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery. 1962 Feb;51(2):224-32.
- Nielsen HJ. Detrimental effects of perioperative blood transfusion. Br J Surg. 1995 May;82(5):582-7. Review.
- Zohar E, Fredman B, Ellis MH, Ifrach N, Stern A, Jedeikin R. A comparative study of the postoperative allogeneic blood-sparing effects of tranexamic acid and of desmopressin after total knee replacement. Transfusion. 2001 Oct;41(10):1285-9.
- EudraCT nr 2006-006714-14
Study Results
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 Detail | No significant events occured after participant enrollment prior to assignment to a group. |
Arm/Group Title | Tranexamic Group | Placebo Group |
---|---|---|
Arm/Group Description | 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 | 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. |
Period Title: Overall Study | ||
STARTED | 50 | 50 |
COMPLETED | 48 | 45 |
NOT COMPLETED | 2 | 5 |
Baseline Characteristics
Arm/Group Title | Tranexamic Group | Placebo Group | Total |
---|---|---|---|
Arm/Group Description | 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 | 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. | Total of all reporting groups |
Overall Participants | 50 | 50 | 100 |
Age (years) [Median (Full Range) ] | |||
Median (Full Range) [years] |
63
|
64.5
|
63
|
Age, Customized (participants) [Number] | |||
<60 years of age |
15
30%
|
15
30%
|
30
30%
|
60-69 years of age |
24
48%
|
17
34%
|
41
41%
|
>=70 years of age |
11
22%
|
18
36%
|
29
29%
|
Sex/Gender, Customized (Count of Participants) | |||
Female |
50
100%
|
50
100%
|
100
100%
|
Region of Enrollment (participants) [Number] | |||
Sweden |
50
100%
|
50
100%
|
100
100%
|
Height (meter) [Median (Full Range) ] | |||
Median (Full Range) [meter] |
1.67
|
1.63
|
1.64
|
Weight (kilogram) [Median (Full Range) ] | |||
Median (Full Range) [kilogram] |
71
|
64.3
|
67.6
|
Body mass index (kg/m^2) [Median (Full Range) ] | |||
Median (Full Range) [kg/m^2] |
25.9
|
24
|
25.1
|
Body mass index (participants) [Number] | |||
Normal weight (BMI<25) |
19
38%
|
31
62%
|
50
50%
|
Overweight (BMI 25-29) |
25
50%
|
14
28%
|
39
39%
|
Obese (BMI >=30) |
6
12%
|
5
10%
|
11
11%
|
Parity (births) [Median (Full Range) ] | |||
Median (Full Range) [births] |
2
|
2
|
2
|
Smokers (participants) [Number] | |||
Number [participants] |
8
16%
|
5
10%
|
13
13%
|
Low-dose aspirin medication (participants) [Number] | |||
Number [participants] |
7
14%
|
5
10%
|
12
12%
|
Cardiac disease (participants) [Number] | |||
Number [participants] |
5
10%
|
1
2%
|
6
6%
|
Arterial hypertension/vascular disease (participants) [Number] | |||
Number [participants] |
22
44%
|
13
26%
|
35
35%
|
Diabetes mellitus (participants) [Number] | |||
Number [participants] |
3
6%
|
7
14%
|
10
10%
|
Previous hysterectomy (participants) [Number] | |||
Number [participants] |
6
12%
|
3
6%
|
9
9%
|
Previous laparotomy (participants) [Number] | |||
Number [participants] |
25
50%
|
21
42%
|
46
46%
|
Predicted Blood Volume (PBV) (liter) [Median (Full Range) ] | |||
Median (Full Range) [liter] |
4.16
|
3.87
|
3.99
|
RBC transfusion preoperatively (participants) [Number] | |||
Number [participants] |
3
6%
|
3
6%
|
6
6%
|
Outcome Measures
Title | Perioperative Bleeding Volume |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Tranexamic Group | Placebo Group |
---|---|---|
Arm/Group Description | 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 | 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. |
Measure Participants | 50 | 50 |
Median (Full Range) [milliliter] |
520
|
730
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Tranexamic Group, Placebo Group |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.03 |
Comments | Statistical significance threshold was p < 0.05 | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | Mann-Whitney U-test, one-sided test |
Title | Number of Patients Receiving Blood Transfusions |
---|---|
Description | Total number of RBC-transfused women in each group |
Time Frame | From start of operation to discharge from hospital, up to 5 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Tranexamic Group | Placebo Group |
---|---|---|
Arm/Group Description | 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 | 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. |
Measure Participants | 50 | 50 |
Number [participants] |
15
30%
|
22
44%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Tranexamic Group, Placebo Group |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.07 |
Comments | Statistical significance threshold was p < 0.05 | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | Mann-Whitney U-test, one-sided test |
Title | Number of Units of Red Blood Cells (RBC) Transfused |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Tranexamic Group | Placebo Group |
---|---|---|
Arm/Group Description | 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 | 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. |
Measure Participants | 50 | 50 |
Number [units] |
38
|
53
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Tranexamic Group, Placebo Group |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.46 |
Comments | Statistical significance threshold was p < 0.05 | |
Method | Wilcoxon (Mann-Whitney) | |
Comments | Mann-Whitney U-test, one-sided test | |
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 0.44 | |
Confidence Interval |
(1-Sided) 95% to 0.97 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Number of Transfused Units of Red Blood Cells (RBC) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Participants who received RBC transfusions |
Arm/Group Title | The Placebo Group | The Tranexamic Acid Group |
---|---|---|
Arm/Group Description | The group of women receiving saline solution (0.9% NaCl) intravenously immediately before the surgery 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 skin incision at surgery. | The group of women receiving Tranexamic acid intravenously immediately before the surgery 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 skin incision at surgery |
Measure Participants | 22 | 15 |
Median (Full Range) [units] |
2
|
2
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Tranexamic Group, Placebo Group |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.46 |
Comments | p< 0.05 for statistical significance | |
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Number of Patients With Clinically or Radiologically Verified Thromboembolic Events Within 5 Weeks Postoperatively |
---|---|
Description | Thromboembolic events including arterial thrombosis, muscle vein thrombosis, superficial and deep venous thrombosis. |
Time Frame | From time of operation to 5 weeks postoperatively. |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Tranexamic Group | Placebo Group |
---|---|---|
Arm/Group Description | 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 | 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. |
Measure Participants | 50 | 50 |
Count of Participants [Participants] |
2
4%
|
5
10%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Tranexamic Group, Placebo Group |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.22 |
Comments | Statistical significance threshold p-value < 0.05 | |
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
Estimated Value | 0.36 | |
Confidence Interval |
(2-Sided) 95% 0.05 to 2.72 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | Data were collected until five weeks after surgery. | |||
---|---|---|---|---|
Adverse Event Reporting Description | Systematic and non-systematic assessment. | |||
Arm/Group Title | Tranexamic Group | Placebo Group | ||
Arm/Group Description | 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 | 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. | ||
All Cause Mortality |
||||
Tranexamic Group | Placebo Group | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/50 (0%) | 0/50 (0%) | ||
Serious Adverse Events |
||||
Tranexamic Group | Placebo Group | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/50 (20%) | 14/50 (28%) | ||
Infections and infestations | ||||
Postoperative infections | 3/50 (6%) | 3 | 3/50 (6%) | 3 |
Surgical and medical procedures | ||||
Re-operations | 5/50 (10%) | 6 | 6/50 (12%) | 6 |
Vascular disorders | ||||
Thromboembolic events | 2/50 (4%) | 2 | 5/50 (10%) | 5 |
Other (Not Including Serious) Adverse Events |
||||
Tranexamic Group | Placebo Group | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 18/50 (36%) | 17/50 (34%) | ||
General disorders | ||||
Readmissions | 11/50 (22%) | 11 | 4/50 (8%) | 4 |
Infections and infestations | ||||
Postoperative infections | 7/50 (14%) | 7 | 13/50 (26%) | 13 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Professor Dr. Preben Kjölhede |
---|---|
Organization | Department of Obstetrics and Gynaecology, and Department of Clinical and Experimental Medicine, Linköpings universitet (LIU), Sweden |
Phone | +4638231188 |
preben.kjolhede@liu.se |
- EudraCT nr 2006-006714-14