Clinical Trials Register

Summary
EudraCT Number:	2016-001916-39
Sponsor's Protocol Code Number:	AB0001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-08
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-001916-39

A.3

Full title of the trial

A phase IV, single-blind, randomized, controlled, single-center study evaluating the efficacy of amoxicillin+clavulanic acid Vs no treatment in preventing complications after tooth extraction and the efficacy of a probiotic in preventing antibiotic adverse effect

Studio di fase IV randomizzato, controllato, in singolo cieco e monocentrico atto a valutare l¿efficacia di amoxicillina+acido clavulanico VS nessun trattamento nella prevenzione delle complicanze post estrattive e l¿efficacia di un probiotico nella prevenzione degli effetti avversi dell¿antibiotico

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Evaluation of the effectiveness of the antibiotic therapy in preventing complications after tooth extraction and evaluation of the effectiveness of the probiotic in preventing antibiotic adverse effect

Valutazione dell¿efficacia della terapia antibiotica nel prevenire le complicanze dopo estrazione dentaria e dell¿efficacia di un probiotico nel prevenire gli effetti avversi dell¿antibiotico

A.3.2

Name or abbreviated title of the trial where available

AB0001

A.4.1

Sponsor's protocol code number

AB0001

A.5.4

Other Identifiers

Name:

AB0001

Number:

AB0001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	VALEAS SPA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	U.O. Odontostomatologia e Chirurgia del Cavo Orale
B.5.2	Functional name of contact point	U.O. Odontostomatologia e Chirurgia
B.5.3	Address:
B.5.3.1	Street Address	VIA ROMA 67
B.5.3.2	Town/ city	PISA
B.5.3.3	Post code	56126
B.5.3.4	Country	Italy
B.5.4	Telephone number	050992628
B.5.5	Fax number	050992596
B.5.6	E-mail	antonio.barone@unipi.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NEODUPLAMOX - 875 MG/125 MG COMPRESSE RIVESTITE CON FILM 12 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	VALEAS SPA INDUSTRIA CHIMICA E FARMACEUTICA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	NEODUPLAMOX
D.3.2	Product code	NEODUPLAMOX
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AMOXICILLINA TRIIDRATO
D.3.9.1	CAS number	26787-78-0
D.3.9.2	Current sponsor code	AMOXICILLINA TRIIDRATO
D.3.9.3	Other descriptive name	AMOXICILLINA TRIIDRATO
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	875
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POTASSIO CLAVULANATO
D.3.9.1	CAS number	58001-44-8
D.3.9.2	Current sponsor code	POTASSIO CLAVULANATO
D.3.9.3	Other descriptive name	POTASSIO CLAVULANATO
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	125
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

teeth needing extraction due to infections

estrazioni dentali per patologie infettive

E.1.1.1

Medical condition in easily understood language

teeth needing extraction due to infections

estrazioni dentali per patologie infettive

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10062132
E.1.2	Term	Tooth extraction
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10044034
E.1.2	Term	Tooth disorder
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate whether antibiotic therapy could reduce post-surgical complications after tooth extractions due to a dental infection as compared to no-treatment group by which we want to evaluate whether the extraction alone is sufficient to resolve the infection leading to tooth extraction. Besides, it will be important also to understand whether probiotic could be beneficial for the patients in reducing gastro-intestinal side effects of the antibiotics

Valutare se la terapia antibiotica possa ridurre le complicanze post-estrattive dopo estrazione dentaria dovuta a infezioni odontogene, rispetto al gruppo controllo che non ricever¿ nessun farmaco. Il gruppo controllo ¿ necessario per capire se la sola estrazione sia di per s¿ sufficiente a risolvere l¿infezione odontogena. Inoltre, sar¿ importante capire se l¿associazione di un probiotico possa produrre benefici nel ridurre gli effetti avversi gastro-intestinali dell¿antibiotico

E.2.2

Secondary objectives of the trial

To describe demographically the population requiring Hospital Dental Care and to understand what are the main reasons for tooth extractions in order to set up tailored dental health programs

Descrivere demograficamente la popolazione che richiede cure odontoiatriche ospedaliere e capire quali sono le principali ragioni di estrazione dentaria, al fine di preparare programmi di salute dentale specifici.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Female and male patients seeking “Oral Dental Care at UO Odontostomatologia e Chirurgia del Cavo Orale” and needing dental extractions due to an ongoing infection.
- Adult patients (=18 year old)
- Subjects capable of giving informed consent
- Subjects who are women of childbearing potential must agree to utilize a highly effective contraceptive measure throughout the course of the study for the entire duration of the trial and the subsequent 60-day follow-up

- Pazienti maschi e femmine che richiedano cure odontoiatriche presso la U.O. di Odontostomatologia e Chirurgia del Cavo Orale e che necessitino di estrazioni dentali per patologie infettive in atto.
- Pazienti maggiorenni (=18 anni)
- Pazienti in grado di firmare un consenso informato
- Donne in età fertile che accettino di utilizzare metodi contraccettivi altamente efficaci durante il corso dello studio e per i successivi 60 giorni di follow up

E.4

Principal exclusion criteria

- Patients requiring third molar extractions
- General contraindications to oral surgery
- Immunosuppressed or immunocompromised patients
- Patients under therapy with aminobisphosphonates i.v
- Head and neck irradiation
- Pregnancy and breastfeeding
- Uncontrolled diabetes
- Patients suffering from infectious mononucleosis
- Patients suffering from colitis
- Patients suffering from renal failure
- Patients having drug and alcohol dependence
- Psychiatric disorders that contraindicate oral surgery
- Allergy both to penicillin, or other beta-lactams, and probiotic
- Hypersensitivity to active ingredient and to all penicillins
- History of severe immediate hypersensitivity reactions (e.g. anaphylaxis) to other beta-lactam agents (e.g. cephalosporins, carbapenems, monobactams)
- Patients under therapy with methotrexate, probenecid, mycophenolate mofetil, allopurinol
- Patients with history of amox+clav-related jaundice/hepatic failure
- Patients with hyper-sensibility to stearate magnesium, sodium carboxymethylamid A, silica colloidal anhydrous, microcrystal cellulose, titanium dioxide (E171), hypromellose, Macrogol (4000-6000) and dimethicone;
- Patients under therapy with oral anticoagulants;
- Hypersensitivity to all excipients/substances in the probiotic

- Pazienti che necessitano di estrazione di terzi molari
- Controindicazioni generali alla chirurgia
- Pazienti immunosoppressi o immunocompromessi
- Pazienti in terapia con aminobifosfonati i.v
- Pazienti irradiati nel distretto testa/collo
- Pazienti in gravidanza o allattamento
- Pazienti con diabete non controllato
- Pazienti affetti da mononucleosi infettiva
- Pazienti affetti da colite
- Pazienti affetti da insufficienza renale
- Pazienti con dipendenza da droghe o alcool
- Pazienti affetti da disturbi psichiatrici per cui sia controindicata la chirurgia orale
- Allergia alla penicillina, o altri beta-lattamici, e al probiotico
- Ipersensibilità al principio attivo e a tutte le penicilline
- Storia di reazioni di ipersensibilità immediata (es. anafilassi) a altri agenti beta-lattamici (es. cefalosporine, carbapenemi, monobattami)
- Pazienti in terapia con metotrexato, probenecid, micofenolato mofetile, allopurinolo
- Pazienti con storia di ittero/insufficienza epatica dovuta a amoxicillina+acido clavulanico
- Pazienti con ipersensibilità a stearato di magnesio, carbossimetilamido sodico A, silice colloidale anidro, cellulosa microcristallina, diossido di titanio (E171), ipromellosa, macrogol (4000-6000) e dimeticone;
- Pazienti in terapia con anticoagulanti orali;
- Ipersensibilità agli eccipienti/sostanze contenute nel probiotico

E.5 End points

E.5.1

Primary end point(s)

The local signs and symptoms to evaluate are swelling, pain (assessed by the Visual Analogic Scale), presence of abscess, fever, post-extraction dental alveolitis (dry socket) and presence of trismus assessed as maximal mouth opening variation (mm). In addition adverse post-extraction events will be evaluated as follows: chewing impairments (assessed by the Visual Analogic Scale), speaking impairments (assessed by the Visual Analogic Scale), daily oral hygiene maneuvers impairments (assessed by the Visual Analogic Scale) and daily activities alterations (days-off from job/study).Moreover, the patients will be provided with a painkiller’s prescription and they are required to take note of the painkillers needed during the first 7 days)

Per valutare l’efficacia dell’antibiotico, verranno considerati segni locali di infezione come:
¿ Edema
¿ Dolore (valutato attraverso la Visual Analogic Scale, VAS)
¿ Presenza di ascesso
¿ Febbre
¿ Alveolite post-estrattiva
¿ Presenza di trisma (valutato come variazione della massima apertura della bocca espressa in millimetri)
¿ Numero di antinfiammatori assunti durante la prima settimana dopo l’estrazione dentaria
Verranno valutati, inoltre, sintomi post-estrattivi come:
¿ Difficoltà di masticazione (valutata attraverso la Visual Analogic Scale, VAS)
¿ Difficoltà di eloquio (valutata attraverso la Visual Analogic Scale, VAS)
¿ Difficoltà nella realizzazione delle manovre di igiene orale quotidiana (valutata attraverso la Visual Analogic Scale, VAS)
¿ Alterazioni delle normali attività quotidiane (giorni persi a lavoro/scuola)

E.5.1.1

Timepoint(s) of evaluation of this end point

T1- 7 after the tooth extraction; T2- 14 days after the tooth extraction; T3- 21 days after the tooth extraction

Tutti i parametri oggetto di valutazione saranno registrati 7, 14, 21 giorni dopo l’estrazione rispettivamente a T1, T2 e T3

E.5.2

Secondary end point(s)

Besides the main objectives, we could describe demographically the population seeking oral dental care at UO Odontostomatologia e Chirurgia del Cavo Orale. Moreover, it will be possible to understand the main reason for tooth extraction in the population coming to the Hospital

Con i dati raccolti potremmo descrivere demograficamente la popolazione che afferisce alla U.O di Odontostomatologia e Chirurgia del Cavo Orale e comprendere quali siano le ragioni principali di estrazione nei pazienti che ricercano assistenza odontoiatrica ospedaliera

E.5.2.1

Timepoint(s) of evaluation of this end point

T0 (extraction)

T0 (estrazione)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

VALUTATORE IN CIECO

BLIND EVALUATOR

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

NESSUN TRATTAMENTO

NO TREATMENT

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

150

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the participation in the trial the subject could be treated at U.O Odontostomatologia e Chirurgia del Cavo Orale for every other dental need and for every possible problem that will occour as a consequence of the extraction procedure

Dopo la partecipazione alla sperimentazione, i pazienti possono essere trattati presso l¿U.O Odontostomatologia e Chirurgia del Cavo Orale per ogni altra necessit¿ odontoiatrica e per ogni possibile problema conseguente alla procedura di estrazione dentaria.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-09-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-19

P. End of Trial
P.	End of Trial Status	Ongoing

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