Clinical Trial Results:
A Collagen-Fibrin Patch (Tachosil®) for the Prevention of Symptomatic Lymphoceles after Pelvic Lymphadenectomy in Women with Gynecologic Malignancies: a Randomized Clinical Trial
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Summary
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EudraCT number |
2011-003115-34 |
Trial protocol |
AT |
Global end of trial date |
31 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Feb 2021
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First version publication date |
22 Feb 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
V1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01470677 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Medical University of Vienna
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Sponsor organisation address |
Währinger Gürtel 18-20, Vienn, Austria, 1090
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Public contact |
Abtlg f. Gyn. und gyn. Onkologie, Medizinische Universität Wien, 0043 01404002915, alexander.reinthaller@meduniwien.ac.at
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Scientific contact |
Abtlg f. Gyn. und gyn. Onkologie, Medizinische Universität Wien, 0043 01404002915, alexander.reinthaller@meduniwien.ac.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
08 Apr 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary outcome variable was defined as follows: to evaluate the incidence of symptomatic pelvic lymphoceles defined by CTCAE 4.03 grade ≥2 within 4 weeks after surgery in women undergoing open or laparoscopic pelvic lymphadenectomy for cervical, endometrial, or ovarian cancer with and without the application of fibrin-collagen patches during surgery.
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Protection of trial subjects |
In order to ensure adequate application of the patches by laparoscopy, all surgeons must have had performed at least two prior laparoscopic operations during which they rolled the patch around a laparoscopic instrument, moved it through a 10 mm trocar into the abdomen, and flattened it out on the pelvic side wall.
All women underwent a gynecologic examination and a transvaginal and/or transabdominal ultrasound examination at the time of discharge of the hospital. All women were scheduled for a follow-up visit 4 weeks after surgery including a gynecologic examination and a transvaginal and transabdominal ultrasound examination, performed by a physician experienced in transvaginal and transabdominal ultrasound examinations, who had not participated in the original surgical procedure and was blinded to the treatment allocation.
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Background therapy |
All women underwent pelvic lymphadenectomy by open or laparoscopic surgery. The procedures were performed as follows: the peritoneum was incised parallel to the iliac vessels. Then, the iliac vessels were screened for the presence of bulky lymph nodes. If a lymph node debulking was performed, no fibrin-collagen patches were applied. In women with routine pelvic lymphadenectomy, lymph node tissue was removed from the external iliac vessels, the obturator fossa, the interiliac region, and the common iliac region after identification and appropriate preparation of the surgical landmarks, ie iliac vessels, femoral canal, chorda, and obturator nerve. At the end of the procedure, hemostasis was checked and a fibrin-collagen patch of 4.8x4.8 cm was attached to the obturator fossa and another patch of 4.8x4.8 cm to the femoral canal of each side of the pelvic side wall in the intervention group. In the control group, no fibrin-collagen patches were used. No specific drainage of the retroperitoneum was performed. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 46
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Country: Number of subjects enrolled |
Germany: 20
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Country: Number of subjects enrolled |
Czechia: 98
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Worldwide total number of subjects |
164
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EEA total number of subjects |
164
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
116
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From 65 to 84 years |
47
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85 years and over |
1
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Recruitment
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Recruitment details |
Inclusion criteria were as follows: open or laparoscopic surgery for cervical, endometrial, or ovarian cancer including bilateral systematic pelvic lymphadenectomy, age between 18 and 70 years, and provision of written informed consent. Exclusion criteria were as follows: a history of previously diagnosed lymph edema. | |||||||||
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Pre-assignment
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Screening details |
173 patients were screened, 9 patients were not eligible due to not meeting inclusion criterias. 164 patients were randomized, 11 patients were lost to follow-up. | |||||||||
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Period 1
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Period 1 title |
baseline period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Assessor [1] | |||||||||
Blinding implementation details |
Women were centrally randomized by one of the investigators (CT). Using the central randomization list, allocation numbers were assigned and sealed in opaque envelopes with consecutive numbers for each center. The envelopes were sent to respective study centers and were opened during surgery after completion of pelvic lymphadenectomy. Outcome assessment was not performed by the surgeon, who had performed the lymphadenectomy and outcome assessors were not aware of the treatment allocation.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Tachosil | |||||||||
Arm description |
At the end of the procedure, hemostasis was checked and a fibrin-collagen patch of 4.8x4.8 cm was attached to the obturator fossa and another patch of 4.8x4.8 cm to the femoral canal of each side of the pelvic side wall in the intervention group | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
tachosil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicated sponge
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Routes of administration |
Intraabdominal use
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Dosage and administration details |
two fibrin-collagen patch of 4.8x4.8 cm were attached to each pelvic sidewalls, i.e. four patches in total.
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Arm title
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Control | |||||||||
Arm description |
In the control group, no fibrin-collagen patches were used. No specific drainage of the retroperitoneum was performed. | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: the trial is single blinded, as the patients were aware whether Tachosil was applied during surgery or not; the ultrasound assessor, which assessed the presence of lymphoceleand if yes the extent of a lymphocele were blinded to the intervention |
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Baseline characteristics reporting groups
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Reporting group title |
Tachosil
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Reporting group description |
At the end of the procedure, hemostasis was checked and a fibrin-collagen patch of 4.8x4.8 cm was attached to the obturator fossa and another patch of 4.8x4.8 cm to the femoral canal of each side of the pelvic side wall in the intervention group | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control
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Reporting group description |
In the control group, no fibrin-collagen patches were used. No specific drainage of the retroperitoneum was performed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tachosil
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Reporting group description |
At the end of the procedure, hemostasis was checked and a fibrin-collagen patch of 4.8x4.8 cm was attached to the obturator fossa and another patch of 4.8x4.8 cm to the femoral canal of each side of the pelvic side wall in the intervention group | ||
Reporting group title |
Control
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Reporting group description |
In the control group, no fibrin-collagen patches were used. No specific drainage of the retroperitoneum was performed. | ||
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End point title |
primary endpoint: symptomatic lymphocele | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
reduction of the incidence of symptomatic lymphoceles within 4 weeks after surgery
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Statistical analysis title |
primary analysis | |||||||||
Statistical analysis description |
presence of symptomatic lymphocele
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Comparison groups |
Tachosil v Control
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Number of subjects included in analysis |
164
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.47 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
12 weeks after surgery
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Assessment type |
Systematic | |||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
tachosil
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Reporting group description |
- | |||||||||||||||
Reporting group title |
control group
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Reporting group description |
- | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: no non-serious adverse events or serious adverse events were observed |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Oct 2012 |
change of the primary endpoint due to a recent publication presenting reliable data on the very important clinical endpoint "symptomatic lymphocele" |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
