Perioperative Management in Gynaecological Carcinoma Surgery

Study Overview
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Brief Summary
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This study is to determine the effect of perioperative treatment with intravenous iron and tranexamic acid on the reduction of intraoperative and postoperative RBC transfusions in gynaecological carcinoma patients undergoing abdominal surgery.

Detailed Description
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Radical abdominal surgery often leads to intraoperative bleeding frequently exceeding 1000 ml and approximately 50% of women undergoing this surgery require blood transfusion. Perioperative blood transfusions have been shown to increase of length of stay, surgical complications, postoperative morbidity and mortality. There are a few data on the reduction in red blood cell count (RBC) transfusions using perioperative management with intravenous iron and tranexamic acid in women with gynaecological carcinoma surgery. This study is to determine the effect of perioperative treatment with intravenous iron and tranexamic acid on the reduction of intraoperative and postoperative RBC transfusions in gynaecological carcinoma patients undergoing abdominal surgery.

Official Title
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Perioperative Management With Ferric Carboxymaltose and Tranexamic Acid to Reduce Transfusion Rate in Gynaecological Carcinoma Surgery: a Single-blind, Mono-centre, Randomized Trial

Conditions
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Gynaecological Carcinoma

Intervention / Treatment
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* Drug: ferric carboxymaltose
* Drug: tranexamic acid
* Drug: ferric carboxymaltose and tranexamic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent as documented by signature women with gynaecological carcinoma surgery with hemoglobin level between 90-120 g/I and serum ferritin < 100 µg/I (or ferritin index < 3.19) at recruitment pregnancy test negative in women younger than 50 years Exclusion Criteria: known hypersensitivity or allergy to ferric carboxymaltose or tranexamic acid history or present laboratory signs of bleeding disorders, coagulopathy or thromboembolic events history of myocardial infarction within the last year, present unstable angina or severe coronary disease increased plasma creatinine levels above 250 µmol/I inability to follow the procedures of the study (language problems, severe psychiatric or mental disorders) iron overload current administration of intravenous iron or previous intravenous iron therapy or blood transfusion within three months date of scheduled surgery is outside 28 days after the date of recruitment other clinically significant concomitant disease states (e.g., hepatic dysfunction, cardiovascular disease, etc.) participation in another study with investigational drug within the 30 days enrolment of the investigator, his/her family members, employees and other dependent persons.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ferric carboxymaltose<br>ferric carboxymaltose 20 mg/kg (with a maximum dose of 1000 mg ferric carboxymaltose in a single Infusion) (Ferinject® 1000 mg/20 ml) will be administered between day -27 and day -7. | Drug: ferric carboxymaltose<br>* Ferric carboxymaltose 20 mg/kg (with a maximum dose of 1000 mg ferric carboxymaltose in a single Infusion) (Ferinject® 1000 mg/20ml, Vifor (International) AG, St. Gallen, Switzerland) will be diluted in 250 ml of 0.9% m/V sodium chloride solution and administered over 15 minutes intravenously between day -27 and day -7. The colour of ferric carboxymaltose is dark brown. A single Ferinject administration should not exceed 20 mg iron/kg body weight.<br>|
| Experimental: tranexamic acid<br>tranexamic acid 10mg/kg (Tranexam OrPha 1000 mg/10 ml, OrPha Swiss GmbH, Küsnacht, Switzerland) will be administered 15 -30 minutes prior to surgery followed by infusion of tranexamic acid through syringe pump (1 mg/kg/h) till 4 h postoperatively | Drug: tranexamic acid<br>* Tranexamic acid 10mg/kg (Tranexam OrPha 1000 mg/10 ml, OrPha Swiss GmbH, Küsnacht, Switzerland) will be administered 15 -30 minutes prior to surgery followed by infusion of tranexamic acid through syringe pump (1 mg/kg/h) till 4 h postoperatively. The colour of the medicament is transparent.<br>|
| Experimental: ferric carboxymaltose and tranexamic acid<br>ferric carboxymaltose (Ferinject® 1000 mg/20 ml) between day -27 and day -7 and tranexamic acid (Tranexam OrPha 1000 mg/10 ml) 15-30 minutes prior to surgery followed by Infusion of tranexamic acid through syringe pump (1 mg/kg/h) till 4 h postoperatively will be administered. | Drug: ferric carboxymaltose and tranexamic acid<br>* Ferric carboxymaltose (Ferinject® 1000 mg/20 ml) will be administered between day -27 and day -7 and tranexamic acid (Tranexam OrPha 1000 mg/10 ml) 15-30 minutes prior to surgery followed by infusion of tranexamic acid through syringe pump (1 mg/kg/h) till 4 h postoperatively.<br>|
| No Intervention: no treatment accordingly current standard of care<br>no treatment accordingly current standard of care will be given | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of all perioperative (intraoperative and postoperative) administered RBC transfusions | number of all perioperative (intraoperative and postoperative) administered RBC transfusions (the absolute rate of RBC transfusions) | day of surgery until follow up visit 5 (up to 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in hemoglobin level | change in hemoglobin level (g/dl) | day of surgery until follow up visit 5 (up to 28 days) | 
| rate of transfused women with gynaecological carcinoma during and/or after surgery | rate of transfused women with gynaecological carcinoma during and/or after surgery | day of surgery until follow up visit 5 (up to 28 days) | 
| blood loss measured during surgery (ml) | blood loss measured during surgery (ml) | day of surgery | 
| rate of other blood product transfusions | rate of other blood product transfusions (fresh frozen plasma, autologous whole blood) | day of surgery until follow up visit 5 (up to 28 days) | 
| requirement of additional local or systematic haemostatic therapy (descriptive) | requirement of additional local or systematic haemostatic therapy (descriptive) | day of surgery until follow up visit 5 (up to 28 days) | 
| duration of surgery (minutes) | duration of surgery (minutes) | day of surgery | 
| duration of hospitalisation (days) | duration of hospitalisation (days) | from admission to discharge date (up to 56 days) | 
| number of postoperative complications | number of postoperative complications: abdominal pain, haemorrhage, reoperation owing to bleeding, wound infection, pulmonary complications, postoperative renal dysfunction, systemic sepsis | day of surgery until follow up visit 5 (up to 28 days) | 
| postoperative mortality | postoperative mortality | day of surgery until follow up visit 5 (up to 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ferric carboxymaltose, tranexamic acid, RBC transfusion