Clinical Trial Results:
Treatment of hypertrophic scars using needle-free jet-injection of triamcinolone and 5-Fluorouracile: a prospective, controlled, randomized, single-blinded split-lesion trial.
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Summary
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EudraCT number |
2019-001066-15 |
Trial protocol |
DK |
Global end of trial date |
17 Mar 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Nov 2021
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First version publication date |
27 Nov 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 |
LR19912019
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
De Videnskabsetiske Komiteer for Region Hovedstade: H-19024719 | ||
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Sponsors
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Sponsor organisation name |
Merete Hædersdal
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Sponsor organisation address |
Nielsine Nielsens Vej 17, opgang 9, 2 sal, Copenhagen NV, Denmark, 2400
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Public contact |
Department of Dermatology, Bispebjerg Hospital, 0045 3635000, Katrine.togsverd-bo@regionh.dk
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Scientific contact |
Department of Dermatology, Bispebjerg Hospital, 0045 3635000, Katrine.togsverd-bo@regionh.dk
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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 |
20 Sep 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Mar 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Mar 2020
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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 |
• Blinded, on-site, clinical evaluation of mean change in HTS height following jet-injections with TAC+5-FU at baseline and 4 weeks (+/- 5 days) after intervention, by Vancouver Scar Scale height (VSSheight).
• Blinded, on-site, clinical evaluation of mean change in HTS appearance following jet-injections with TAC+5-FU at baseline and 4 weeks (+/- 7 days) after intervention, by full Vancouver Scar Scale (VSStotal).
• Mean change in blinded, evaluation of clinical photos by off-site, clinical experts. evaluation of clinical photos of treated scar site, at baseline and 4 weeks (+/- 7 days) after intervention, and treated vs. untreated scar sites 4 weeks (+/- 7 days) from intervention, using the Visual Analogue Scale (VAS)
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Protection of trial subjects |
All intrested patients was invited to a preliminary informational screening visit at which they recceived comprehensive oral information on the study by the primary investigator, Merete Hædersdal, and written information was handed out. All Patients was informed both verbally and in written form about risks and possible side-effects of all tests/treatments offered. The meeting took place in a separate office to ensure a safe and calm environment. The patients was specifically informed that they can bring one or more assessors to all meetings and interventions if they so choose. Each patient was evaluated by the investigator to assess the suitability of entering the study.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Apr 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Denmark: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
20
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment to begin and study interventions 1. September 2019. Last patient last visit: 1 march. 2020. End of study: 15. march 2020. All potential patients was recruited from the Department of Dermatology, Bispebjerg Hospital | |||||||||
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Pre-assignment
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Screening details |
14 patients was excluted due to: History of, or presenting with a keloid scar / Use of topical treatment in the last 6 months and lack of willingness to refrain use during the trial as topical treatment / Anti Coagulatory Treatment. | |||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind [1] | |||||||||
Roles blinded |
Assessor, Investigator [2] | |||||||||
Blinding implementation details |
Included HTS will be split into two halves. Each scar half will be assigned to jet-injection treatment or serve as untreated control according to a balanced randomization. Randomization will be conducted with consecutively numbered, closed, non- transparent envelopes containing a computer-generated allocation. The envelopes will be prepared by a third party to ensure allocation concealment, taken to use in a numeric order and opened just before the jet-injection treatment.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Untreated. | |||||||||
Arm description |
Half of the HTS (scar) that was allocated to untreated / control did now reccive the active treatment. | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Treatment | |||||||||
Arm description |
The half of the scar allocated to treatment. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Triamcinolone acetonide
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Investigational medicinal product code |
Triamcinolone acetonide
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Other name |
Kenalog
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Pharmaceutical forms |
Suspension for injection in multidose container
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Routes of administration |
Subdermal use
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Dosage and administration details |
1 part TAC 10 or 40 mg/ml (Kenalog®, Bristol-Myers Squibb, Denmark) and 9 parts 5-FU 50 mg/mg (Fluorouracil “Accord”, Accord Healthcare Limited, England). Strength of TAC will be clinically based on the HTS and the atrophic potential and/or anatomical location. A maximum of 80 mg TAC or 100 mg 5-FU will be used in the treatment session
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Investigational medicinal product name |
Fluorouracil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in multidose container
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Routes of administration |
Subdermal use
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Dosage and administration details |
1 part TAC 10 or 40 mg/ml (Kenalog®, Bristol-Myers Squibb, Denmark) and 9 parts 5-FU 50 mg/mg (Fluorouracil “Accord”, Accord Healthcare Limited, England). Strength of TAC will be clinically based on the HTS and the atrophic potential and/or anatomical location. A maximum of 80 mg TAC or 100 mg 5-FU will be used in the treatment session
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| Notes [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: Included HTS will be split into two halves. Each scar half will be assigned to jet-injection treatment or serve as untreated control according to a balanced randomization. The scar part located the furthest to the left (from the patient’s perspective) is referred to as lesion 1, the scar part further to the right as lesion 2. If the scar is vertically arranged, the upper wound part is referred to as lesion 1 and the lower one as lesion 2. Lesion 1 and 2 will be randomized for jet-injection treat [2] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Included HTS will be split into two halves. Each scar half will be assigned to jet-injection treatment or serve as untreated control according to a balanced randomization. The scar part located the furthest to the left (from the patient’s perspective) is referred to as lesion 1, the scar part further to the right as lesion 2. If the scar is vertically arranged, the upper wound part is referred to as lesion 1 and the lower one as lesion 2. Lesion 1 and 2 will be randomized for jet-injection treat |
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Baseline characteristics reporting groups
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Reporting group title |
Overall
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Reporting group description |
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End points reporting groups
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Reporting group title |
Untreated.
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Reporting group description |
Half of the HTS (scar) that was allocated to untreated / control did now reccive the active treatment. | ||
Reporting group title |
Treatment
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Reporting group description |
The half of the scar allocated to treatment. | ||
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End point title |
Vancouver Scar Scale height (VSSheight) | ||||||||||||||||||||||||
End point description |
linded, on-site, clinical evaluation of mean change in HTS appearance following jet- injections with TAC+5-FU at baseline and 4 weeks (+/- 7 days) after intervention, by full Vancouver Scar Scale (VSStotal), to evaluate the potential clinical effect on the scar parameters: vascularity, pigmentation, pliability and height
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End point type |
Primary
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End point timeframe |
At baseline and follow-up 4 weeks (+/- 7 days)
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Statistical analysis title |
Wilcoxon signed-rank test | ||||||||||||||||||||||||
Statistical analysis description |
A sample size of 16 patients provided 90% power to detect a clinical change of 50% in VSS height with an α = 0.05. A 20% attrition rate against dropout was chosen, and 20 patients were included. Descriptive statistics and tables are presented as medians or means with interquartile ranges (IQR) and standard deviations (SD), unless otherwise stated. Wilcoxon signed-rank test was used to compare baseline and follow-up data. Level of significance = p<0.05. Statistical analysis was performed using SP
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Comparison groups |
Untreated. v Treatment
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
SAEs are reported within 24 hours to sponsor-investigator Merete Hædersdal. At the end of the trial, a final report with all AEs, ARs, SAEs and SUSARs is handed to the Danish Health and Medicine Authority and the Regional Committee on Health Research Ethi
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Adverse event reporting additional description |
The investigators are responsible for routine assessments of AEs and ARs. All clinical complaints, symptoms or signs that meet AE or AR definitions will be documented in the study record and the participant’s medical record.
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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 |
22
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Reporting groups
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Reporting group title |
Adverse events
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Reporting group description |
Three patients experienced mild AE. | ||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
