Tranexamic Acid in Surgery of Advanced Ovarian Cancer

Sponsor
Preben Kjolhede, MD, professor (Other)
Overall Status
Completed
CT.gov ID
NCT00740116
Collaborator
(none)
100
3
2
51
33.3
0.7

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
  • Drug: Tranexamic acid
  • Drug: 0.9% NaCl solution
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Tranexamic Acid in Surgery of Advanced Ovarian Cancer - a Prospective Randomized Double Blind Placebo Controlled Study
Study Start Date :
Mar 1, 2008
Actual Primary Completion Date :
Jun 1, 2012
Actual Study Completion Date :
Jun 1, 2012

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:
  • Cyklokapron
  • ATC-code B02AA02
  • 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:
  • 0.9 % sodium chloride
  • ATC-code B05BB01
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    2. 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

    3. 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

    4. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts 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.

    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

    Responsible Party:
    Preben Kjolhede, MD, professor, Associate professor, University Hospital, Linkoeping
    ClinicalTrials.gov Identifier:
    NCT00740116
    Other Study ID Numbers:
    • EudraCT nr 2006-006714-14
    First Posted:
    Aug 22, 2008
    Last Update Posted:
    Mar 15, 2022
    Last Verified:
    Jan 1, 2022
    Keywords provided by Preben Kjolhede, MD, professor, Associate professor, University Hospital, Linkoeping
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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
    5. Secondary Outcome
    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

    The study was not powered for postoperative complications in general. Only 56% of the women participated in the duplex ultrasound assessment of the legs, which was an optional investigation according to the trial protocol. This indicates a risk of bias for the outcome of thromboembolic complications.

    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
    Email preben.kjolhede@liu.se
    Responsible Party:
    Preben Kjolhede, MD, professor, Associate professor, University Hospital, Linkoeping
    ClinicalTrials.gov Identifier:
    NCT00740116
    Other Study ID Numbers:
    • EudraCT nr 2006-006714-14
    First Posted:
    Aug 22, 2008
    Last Update Posted:
    Mar 15, 2022
    Last Verified:
    Jan 1, 2022