Clinical Trial Results:
Efficacy of DC071 mouthwash (0,2 % chlorhexidine digluconate) in peri-surgical care for preventing alveolar osteitis after third molar extraction.
Prospective, multicenter, randomised, double-blind, placebo controlled study in parallel groups
Summary
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EudraCT number |
2014-004682-24 |
Trial protocol |
EE LV LT FR ES |
Global end of trial date |
17 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Nov 2018
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First version publication date |
30 Nov 2018
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Other versions |
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 |
DC0071BB405
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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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Sponsors
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Sponsor organisation name |
Pierre Fabre Medicament
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Sponsor organisation address |
45 Place Abel Gance, Boulogne, France, 92100
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Public contact |
Centre de Recherche et Développement Pierre Fabre, Karim KEDDAD, MD, +33 (0)534506250, karim.keddad@pierre-fabre.com
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Scientific contact |
Centre de Recherche et Développement Pierre Fabre, Karim KEDDAD, MD, +33 (0)534506250, karim.keddad@pierre-fabre.com
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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 |
02 Jun 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Feb 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Feb 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 |
To demonstrate the efficacy of chlorhexidine mouthwash in the prevention of alveolar osteitis following third molar extraction.
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Protection of trial subjects |
The study was conducted according to Good Clinical Practice (GCP) (CPMP/ICH/135/95), the principles stated in the Declaration of Helsinki (1964) and its subsequent amendments thereto, and national regulations.
The request for authorization by the Competent Authority or its notification (depending on National Régulations) was carried out by the Sponsor.
The study protocol and related documents, including the informed consent forms (ICFs), were submitted for approval to independent, local or national Independent Ethics Committees (IECs) and to competent authorities (CAs) before the study set-up, according to national regulations.
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Background therapy |
In the context of management of post-surgical care, the following medications were to be systematically prescribed to limit post-operative oedema and pain: •Corticosteroids and level-2 analgesics (tramadol or paracetamol associated with codeine) were to be prescribed at a fixed dose during the first 48 hours post-surgery and progressively reduced over the subsequent 48 hours. | ||
Evidence for comparator |
Alveolar osteitis (AO), or dry socket, is one of the most common postoperative complications following the extraction or surgical removal of a tooth. It is defined as postoperative pain inside and around the extraction site, which increases in severity at any time between the first and third day after extraction, accompanied by a partial or total disintegrated blood clot within the alveolar socket, with or without halitosis. Antibacterial agents have been reported to reduce the incidence of AO and CHX digluconate is the most commonly used in dentistry and its efficacy has been widely validated. The use of a placebo was medically acceptable because all patients were followed by the investigator, informed that they may receive a placebo, and treated appropriately if needed | ||
Actual start date of recruitment |
30 Jan 2015
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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 |
Estonia: 131
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Country: Number of subjects enrolled |
France: 72
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Country: Number of subjects enrolled |
Latvia: 103
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Country: Number of subjects enrolled |
Lithuania: 103
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Worldwide total number of subjects |
409
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EEA total number of subjects |
409
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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) |
409
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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 |
A total of 414 patients requiring an impacted mandibular third molar extraction were selected/enrolled, 413 of them randomised (206 patients in the DC071 group and 207 in the placebo group) and 409 were treated. 41 centres in 4 countries (France, Estonia, Lithuania and Latvia) were initiated, of which, 33 were active (selected at least 1 patient). | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 417 patients were screened for study participation and signed an ICF. Of these, 3 patients were not enrolled (could not commit to the study agenda, consent withdrawal) and 1 patient was enrolled but not randomised. Women were included in the last week of their menstrual cycle in order to perform surgery with lower oestrogen level. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||||
Blinding implementation details |
A randomisation list was established by the Clinical Pharmacy Department of the IRPF. This list was computer-generated with validated internal software. The randomisation methodology was validated by the Biometry Department of IRPF before generation. DC071 and placebo were formulated in mouthwash solutions identical in presentation (same size, same colour).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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DC071 | |||||||||||||||||||||||||||
Arm description |
206 patients were randomised in the DC071 arm for seven days (Day -1 to Day 6). Of the 206 randomised patients, 203 of them received at least one dose treatment and 188 patients completed the treatment phase. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
DC071
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Investigational medicinal product code |
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Other name |
Chlorhexidine digluconate 0.2%
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Pharmaceutical forms |
Mouthwash
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Routes of administration |
Buccal use
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Dosage and administration details |
The DC071 mouthwashes (0.2% CHX digluconate) were ready for use and were to be used pure and undiluted. The teeth were to be brushed prior to each use and the mouth then rinsed thoroughly with water before using the mouthwash.
Patients rinsed with 10 mL for 1 min twice daily (in the morning and evening) for 7 days (Day -1 to Day 6).
Patients began taking the mouthwash treatment the day prior (Day -1) to surgical extraction of the mandibular third molar (Visit 3, Day 1). On the day of the surgery (Day 1), the mouthwash treatment was performed in the morning just before the start of surgery (at the investigational centre) and in the evening (with a passive rinsing).
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
207 patients were randomised in the Placebo arm for seven days (Day -1 to Day 6). Of the 207 randomised patients, 206 of them received at least one dose treatment and 185 patients completed the treatment phase. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Mouthwash
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Routes of administration |
Buccal use
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Dosage and administration details |
The placebo mouthwashes were ready for use and were to be used pure and undiluted. The teeth were to be brushed prior to each use and the mouth then rinsed thoroughly with water before using the mouthwash.
Patients rinsed with 10 mL for 1 min twice daily (in the morning and evening) for 7 days (Day -1 to Day 6).
Patients began taking the mouthwash treatment the day prior (Day -1) to surgical extraction of the mandibular third molar (Visit 3, Day 1). On the day of the surgery (Day 1), the mouthwash treatment was performed in the morning just before the start of surgery (at the investigational centre) and in the evening (with a passive rinsing).
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Baseline characteristics reporting groups
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Reporting group title |
DC071
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Reporting group description |
206 patients were randomised in the DC071 arm for seven days (Day -1 to Day 6). Of the 206 randomised patients, 203 of them received at least one dose treatment and 188 patients completed the treatment phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
207 patients were randomised in the Placebo arm for seven days (Day -1 to Day 6). Of the 207 randomised patients, 206 of them received at least one dose treatment and 185 patients completed the treatment phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DC071
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Reporting group description |
206 patients were randomised in the DC071 arm for seven days (Day -1 to Day 6). Of the 206 randomised patients, 203 of them received at least one dose treatment and 188 patients completed the treatment phase. | ||
Reporting group title |
Placebo
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Reporting group description |
207 patients were randomised in the Placebo arm for seven days (Day -1 to Day 6). Of the 207 randomised patients, 206 of them received at least one dose treatment and 185 patients completed the treatment phase. |
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End point title |
Absence of an alveolar osteitis | ||||||||||||||||||
End point description |
The primary efficacy criterion was binary (success/failure) and was evaluated based on the absence/presence of an AO (alveolitis sicca, dry socket) within 7 days after the extraction of the third molar. A treatment failure was defined as the occurrence of an AO within 7 days after the extraction of the third molar.
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End point type |
Primary
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End point timeframe |
The presence of Alveolar osteitis was recorded within 7 days following extraction of the third mandibular molar.
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Statistical analysis title |
Primary analysis | ||||||||||||||||||
Statistical analysis description |
The objective was to test the equality of the proportion between DC071 and placebo (primary hypothesis [H0]: pDC071 = pplacebo against the alternative H1: pDC071 ≠ pplacebo).
The number of patients in failure was compared between DC071 and placebo, on the FAS, using a logistic regression adjusted for treatment, centre and smoker (Yes/No) and with the method of Firth’s penalised likelihood. The Odds Ratio (OR) and the corresponding 95% Wald CI were provided as a measure of the treatment effect.
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Comparison groups |
DC071 v Placebo
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Number of subjects included in analysis |
405
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||
P-value |
= 0.074 | ||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||
Confidence interval |
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95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
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upper limit |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were reported from the enrollment of patients to the end of study visit (Day 8 or Day 9 exceptionally)
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Adverse event reporting additional description |
At each visit, the occurrence of AEs since the last visit was determined by the patient’s spontaneous reporting, the investigator’s non-leading questioning and his/her clinical evaluation. The occurrence of Alveolar Osteitis and any related signs (pain, halitosis, swelling, etc.) were not reported as AEs.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
DC071
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 0.5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |