Clinical Trial Results:
Ensayo clínico multicéntrico, aleatorizado y controlado con placebo para evaluar la eficacia de la utilización perioperatoria de ácido tranexámico sobre la hemorragia quirúrgica en la cirugía compleja de columna. Clinical trial, multicenter, randomized and placebo controlled to evaluate the efficacy of the peri-operative use of tranexamic acid on surgical bleeding in major spinal surgery

Trial information Top of page
Trial identification
Sponsor protocol code	TRANEX2009
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01136590
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	VHIR
Sponsor organisation address	Passeig Vall Hebron 119-129, Barcelona, Spain, 08035
Public contact	Joaquin Lopez-Soriano, VHIR, joaquin.lopez.soriano@vhir.org
Scientific contact	Maria José Colomina Soler, VHIR, mjcolomina@vhebron.net
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	29 May 2014
Is this the analysis of the primary completion data?	Yes
Primary completion date	29 May 2014
Global end of trial reached?	Yes
Global end of trial date	29 May 2014
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	This study was designed to investigate the hypothesis that TXA reduces perioperative blood loss and transfusion requirements in patients undergoing major spine procedures.
Protection of trial subjects	Preoperative administration of i.v. iron or erythropoietin to optimise the haemoglobin concentrations was recorded. All centres used the same protocol for this purpose.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	01 Sep 2010
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Spain: 96
Worldwide total number of subjects	96
EEA total number of subjects	96
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	50
From 65 to 84 years	46
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Patients were recruited at Hospital Clínic (Barcelona), Hospital Universitari Bellvitge (Barcelona), Hospital Universitari Vall d’Hebron (Barcelona), and Hospital de Getafe (Madrid, Spain).
Pre-assignment
Screening details	-
Pre-assignment period milestones
Number of subjects started	96
Number of subjects completed	96
Period 1
Period 1 title	All the study (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator
Arms
Are arms mutually exclusive	Yes
Arm title	TXA iv
Arm description	TXA administration
Arm type	Experimental
Investigational medicinal product name	Tranexamic acid
Investigational medicinal product code
Other name	Amchafibrin
Pharmaceutical forms	Suspension for injection
Routes of administration	Intravenous use
Dosage and administration details	Intravenous infusion of 10mg/kg was administered for 20min before the surgical incision, followed by perfusion of 2mg/kg up tosurgical wound closure at completion of surgery.
Arm title	Placebo
Arm description	-
Arm type	Placebo
Investigational medicinal product name	Saline
Investigational medicinal product code
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	Same volume than TXA group
Number of subjects in period 1 TXA iv Placebo Started 44 52 Completed 44 51 Not completed 0 1      Consent withdrawn by subject - 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	All the study
Reporting group description	-
Reporting group values All the study Total Number of subjects 96 96 Age categorical Units: Subjects     Adults (18-64 years) 20 20     From 65-84 years 76 76 Age continuous Units: years     arithmetic mean (full range (min-max)) 54.5 (18 to 75) - Gender categorical Units: Subjects     Female 67 67     Male 29 29
Subject analysis sets
Subject analysis set title	TXA vs placebo
Subject analysis set type	Full analysis
Subject analysis set description	TXA vs placebo comparison
Subject analysis sets values TXA vs placebo Number of subjects 95 Age categorical Units: Subjects     Adults (18-64 years) 20     From 65-84 years 75 Age continuous Units: years     arithmetic mean (full range (min-max)) 54.5 (18 to 75) Gender categorical Units: Subjects     Female 66     Male 29

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	TXA iv
Reporting group description	TXA administration
Reporting group title	Placebo
Reporting group description	-
Subject analysis set title	TXA vs placebo
Subject analysis set type	Full analysis
Subject analysis set description	TXA vs placebo comparison

End points Top of page

Primary: Total number of transfusion units required Top of page
End point title	Total number of transfusion units required
End point description
End point type	Primary
End point timeframe	Up to postoperative day seven
End point values TXA iv Placebo Number of subjects analysed 44 51 Units: Units     number (confidence interval 95%) 0.85 (0.54 to 1.33) 1.42 (0.97 to 2.08)
Statistical analysis title	RBC units
Comparison groups	TXA iv v Placebo
Number of subjects included in analysis	95
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.06
Method	t-test, 2-sided
Parameter type	Geometrical mean
Confidence interval

Primary: Total number of transfusion units required Top of page

Secondary: Total Blood loss Top of page
End point title	Total Blood loss
End point description
End point type	Secondary
End point timeframe	Up to postoperative day seven
End point values TXA iv Placebo Number of subjects analysed 44 51 Units: millilitre(s)     number (confidence interval 95%) 1695 (1499 to 1916) 2112 (1878 to 2375)
Statistical analysis title	TBL ml
Comparison groups	TXA iv v Placebo
Number of subjects included in analysis	95
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.01
Method	t-test, 2-sided
Parameter type	Geometrical mean
Confidence interval

Secondary: Total Blood loss Top of page

Secondary: Intraoperative blood loss Top of page
End point title	Intraoperative blood loss
End point description
End point type	Secondary
End point timeframe	Up to postoperative day seven
End point values TXA iv Placebo Number of subjects analysed 44 51 Units: millilitre(s)     geometric mean (confidence interval 95%) 1695 (1499 to 1916) 2112 (1878 to 2375)
Statistical analysis title	TBL ml
Comparison groups	TXA iv v Placebo
Number of subjects included in analysis	95
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.01
Method	t-test, 2-sided
Parameter type	Geometrical mean
Confidence interval

Secondary: Intraoperative blood loss Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	During all the study
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	14.1
Reporting groups
Reporting group title	TXA iv
Reporting group description	-
Reporting group title	Placebo
Reporting group description	-
Serious adverse events TXA iv Placebo Total subjects affected by serious adverse events      subjects affected / exposed 2 / 44 (4.55%) 1 / 51 (1.96%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events 0 0 Vascular disorders Venous thromboembolism      subjects affected / exposed 2 / 44 (4.55%) 1 / 51 (1.96%)      occurrences causally related to treatment / all 0 / 2 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Hepatobiliary disorders Cholecystitis      subjects affected / exposed 0 / 44 (0.00%) 1 / 51 (1.96%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events TXA iv Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 24 / 44 (54.55%) 31 / 51 (60.78%) Hepatobiliary disorders Liver function parameters      subjects affected / exposed 24 / 44 (54.55%) 31 / 51 (60.78%)      occurrences all number 24 31 Renal and urinary disorders Impaired renal function      subjects affected / exposed 2 / 44 (4.55%) 0 / 51 (0.00%)      occurrences all number 2 0

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
Further studies are needed to find the optimal TXA dose, with attention to the pharmacokinetics of this drug
Online references
http://www.ncbi.nlm.nih.gov/pubmed/28203735

More information Top of page