Trial Outcomes & Findings for TASALL - TachoSil® Against Liquor Leak (NCT NCT01355627)

Last Updated: 2014-07-25

Results Overview

An assessment was performed daily from randomization to Day of Discharge and at the Efficacy Follow-up visit at week 7 ± 1 week. Clinically evident cerebrospinal fluid leak was confirmed by: 1. Glucose concentration test and/or 2. β-2-transferrin test. A clinically evident pseudomeningocele was considered to be present post-operatively if the following criteria were fulfilled: 1. A subcutaneous, visible/palpable fluctuant fluid accumulation was noted at the site of the surgical incision or adjacent to it; 2. It is suspected the fluid accumulation is cerebrospinal fluid. A treatment failure was defined as application of a new and/or different treatment after application of the study treatment or a third application of (or part of) the selected study treatment on the outside of the dura.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

726 participants

Primary outcome timeframe

Up to 8 Weeks (7 Weeks ± 1 Week)

Results posted on

2014-07-25

Participant Flow

Participants took part in the study at thirty-five Centres in a total of 10 countries: Belgium, France, Germany, Greece, Italy The Netherlands, Poland, Russia, Spain and Sweden from 28 April 2011 to 27 June 2013.

Participants requiring dura sealing techniques for the prevention of post-operative cerebrospinal fluid (CSF) leaks were enrolled; 726 participants were randomized equally in 1 of 2 treatment groups, TachoSil® or Current practice group.

Participant milestones

Participant milestones
Measure	TachoSil® Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. TachoSil® was applied under aseptic conditions during the closure of the dura.	Current Practice Group Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. In addition to primary suture, whatever means of dura closure treatment, alone or in combination, as deemed necessary by the investigator was used with the exception of TachoSil®.
Overall Study STARTED	362	364
Overall Study Safety Analysis Set	362	364
Overall Study Full Analysis Set	361	365
Overall Study COMPLETED	329	326
Overall Study NOT COMPLETED	33	38

Reasons for withdrawal

Reasons for withdrawal
Measure	TachoSil® Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. TachoSil® was applied under aseptic conditions during the closure of the dura.	Current Practice Group Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. In addition to primary suture, whatever means of dura closure treatment, alone or in combination, as deemed necessary by the investigator was used with the exception of TachoSil®.
Overall Study Request By the Patient to Discontinue	5	7
Overall Study Lost to Follow-up	8	7
Overall Study Fatal Adverse Event	19	23
Overall Study Other	1	1

Baseline Characteristics

TASALL - TachoSil® Against Liquor Leak

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TachoSil® n=361 Participants Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. TachoSil® was applied under aseptic conditions during the closure of the dura.	Current Practice Group n=365 Participants Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. In addition to primary suture, whatever means of dura closure treatment, alone or in combination, as deemed necessary by the investigator was used with the exception of TachoSil®.	Total n=726 Participants Total of all reporting groups
Age, Continuous	53.1 years STANDARD_DEVIATION 13.80 • n=5 Participants	53.2 years STANDARD_DEVIATION 14.22 • n=7 Participants	53.1 years STANDARD_DEVIATION 14.00 • n=5 Participants
Age, Customized 18-65 years	288 participants n=5 Participants	293 participants n=7 Participants	581 participants n=5 Participants
Age, Customized >65 years	73 participants n=5 Participants	72 participants n=7 Participants	145 participants n=5 Participants
Sex: Female, Male Female	233 Participants n=5 Participants	211 Participants n=7 Participants	444 Participants n=5 Participants
Sex: Female, Male Male	128 Participants n=5 Participants	154 Participants n=7 Participants	282 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	355 participants n=5 Participants	361 participants n=7 Participants	716 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	55 participants n=5 Participants	62 participants n=7 Participants	117 participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic and Non-Latino	295 participants n=5 Participants	289 participants n=7 Participants	584 participants n=5 Participants
Race/Ethnicity, Customized Unknown	11 participants n=5 Participants	14 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Belgium	87 participants n=5 Participants	87 participants n=7 Participants	174 participants n=5 Participants
Region of Enrollment Germany	33 participants n=5 Participants	29 participants n=7 Participants	62 participants n=5 Participants
Region of Enrollment Spain	54 participants n=5 Participants	54 participants n=7 Participants	108 participants n=5 Participants
Region of Enrollment France	24 participants n=5 Participants	26 participants n=7 Participants	50 participants n=5 Participants
Region of Enrollment Greece	34 participants n=5 Participants	38 participants n=7 Participants	72 participants n=5 Participants
Region of Enrollment Italy	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Netherlands	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Poland	59 participants n=5 Participants	61 participants n=7 Participants	120 participants n=5 Participants
Region of Enrollment Russian Federation	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Sweden	44 participants n=5 Participants	46 participants n=7 Participants	90 participants n=5 Participants
Height	167.4 cm STANDARD_DEVIATION 9.44 • n=5 Participants	168.5 cm STANDARD_DEVIATION 9.18 • n=7 Participants	168.0 cm STANDARD_DEVIATION 9.32 • n=5 Participants
Weight	73.6 kg STANDARD_DEVIATION 14.40 • n=5 Participants	75.2 kg STANDARD_DEVIATION 16.79 • n=7 Participants	74.4 kg STANDARD_DEVIATION 15.65 • n=5 Participants
Body Mass Index (BMI)	26.20 kg/m^2 STANDARD_DEVIATION 4.44 • n=5 Participants	26.42 kg/m^2 STANDARD_DEVIATION 5.10 • n=7 Participants	26.31 kg/m^2 STANDARD_DEVIATION 4.79 • n=5 Participants
Fertility Status Fertile	74 participants n=5 Participants	74 participants n=7 Participants	148 participants n=5 Participants
Fertility Status Post-Menopausal	140 participants n=5 Participants	111 participants n=7 Participants	251 participants n=5 Participants
Fertility Status Surgically Sterile	19 participants n=5 Participants	26 participants n=7 Participants	45 participants n=5 Participants
Fertility Status Not Applicable	128 participants n=5 Participants	154 participants n=7 Participants	282 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 8 Weeks (7 Weeks ± 1 Week)

Population: Full Analysis Population included all enrolled randomized patients.

Outcome measures

Outcome measures
Measure	TachoSil® n=361 Participants Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. TachoSil® was applied under aseptic conditions during the closure of the dura.	Current Practice Group n=365 Participants Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. In addition to primary suture, whatever means of dura closure treatment, alone or in combination, as deemed necessary by the investigator was used with the exception of TachoSil®.
Percentage of Participants With Clinically Evident Verified Post-Operative Cerebrospinal Fluid Leak or Clinically Evident Pseudomeningocele or Treatment Failure	6.9 percentage of participants Interval 4.5 to 10.1	8.2 percentage of participants Interval 5.6 to 11.5

SECONDARY outcome

Timeframe: Assessment at least once prior to discharge from neurosurgical ward, with the expected discharge from neurosurgical ward after an average of 10 days (Up to 28 Weeks)

Population: Full Analysis Population included all enrolled randomized patients.

Non-clinically evident pseudomeningocele was defined as a cerebrospinal fluid accumulation found on a postoperative computerized tomography (CT) or magnetic resonance imaging (MRI) scan which fulfilled the following criteria according to the radiologist assessment before Day of Discharge: CT Scan-Fluid accumulation seen as Hypodense signal, MRI Scan-Fluid accumulation seen as Hypointense signal in T1-weighted image and/ OR Fluid accumulation seen as Hyperintense signal in T2-weighted image.

Outcome measures

Outcome measures
Measure	TachoSil® n=361 Participants Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. TachoSil® was applied under aseptic conditions during the closure of the dura.	Current Practice Group n=365 Participants Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. In addition to primary suture, whatever means of dura closure treatment, alone or in combination, as deemed necessary by the investigator was used with the exception of TachoSil®.
Percentage of Participants With Post-Surgical Non-Clinically Evident Post-Operative Pseudomeningocele	3.0 percentage of participants Interval 1.5 to 5.4	3.0 percentage of participants Interval 1.5 to 5.3

Adverse Events

TachoSil®

Serious events: 94 serious events

Other events: 92 other events

Deaths: 0 deaths

Current Practice Group

Serious events: 97 serious events

Other events: 102 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	TachoSil® n=362 participants at risk Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. TachoSil® was applied under aseptic conditions during the closure of the dura.	Current Practice Group n=364 participants at risk Primary suture was performed. Duraplasty could be performed at the discretion of the investigator. In addition to primary suture, whatever means of dura closure treatment, alone or in combination, as deemed necessary by the investigator was used with the exception of TachoSil®.
Gastrointestinal disorders Constipation	6.6% 24/362 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.3% 12/364 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	5.2% 19/362 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.4% 16/364 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	3.3% 12/362 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.6% 24/364 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypokalaemia	5.5% 20/362 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.3% 23/364 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Pneumocephalus	5.8% 21/362 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.9% 25/364 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	5.0% 18/362 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.5% 20/364 • Safety data were collected from when the patient signed the Informed Consent Form (ICF) until the Safety Follow-up (Up to 28 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER