Clinical Trials Register

Summary
EudraCT Number:	2021-006514-37
Sponsor's Protocol Code Number:	DOAC-CO
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-08-05
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

2021-006514-37

A.3

Full title of the trial

Haemorrhagic risk of direct oral anticoagulants (DOACs) in patients undergoing oral surgery

Rischio emorragico degli anticoagulantiorali diretti (DOACs) in pazienti da sottoporre ad interventi di chirurgia orale

A.3.1

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

To evaluate the safety and efficacy of delayed interruption of therapy with direct-acting oral anticoagulants (DOACs) in patients undergoing oral surgery classified as having moderate bleeding risk.

Valutare la sicurezza e l’efficacia della ritardata interruzione della terapia con anticoagulanti orali ad azione diretta ( DOACs ) in pazienti da sottoporre ad interventi di chirurgia orale classificati a moderato rischio emorragico.

A.3.2

Name or abbreviated title of the trial where available

DOACs and oral surgery

DOACs e chirurgia orale

A.4.1

Sponsor's protocol code number

DOAC-CO

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	Ente Ecclesiastico Ospedale Generale Regionale “F. Miulli”
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	EE Ospedale Gen.Reg. "F.Miulli"
B.5.2	Functional name of contact point	U.O. Chirurgia Maxillo-Facciale
B.5.3	Address:
B.5.3.1	Street Address	Strada Provinciale n. 127, Acquaviva-Santeramo, Km. 4, 100 70021 Acquaviva delle Fonti (Ba)
B.5.3.2	Town/ city	Acquaviva delle Fonti Bari
B.5.3.3	Post code	70121
B.5.3.4	Country	Italy
B.5.6	E-mail	a.maggi@miulli.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.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb/Pfizer EEIG
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	Eliquis
D.3.2	Product code	[041225032/E]
D.3.4	Pharmaceutical form	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	APIXABAN
D.3.9.2	Current sponsor code	041225095
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	5
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

Patients on direct acting oral anticoagulants (DOACs) who are to undergo oral surgery.

Pazienti in terapia con anticoagulanti orali ad azione diretta (DOACs) che si devono sottoporre a chirurgia orale.

E.1.1.1

Medical condition in easily understood language

Patients on direct acting oral anticoagulants (DOACs) who are to undergo oral surgery.

Pazienti in terapia con anticoagulanti orali ad azione diretta (DOACs) che si devono sottoporre a chirurgia orale.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	HLGT
E.1.2	Classification code	10007521
E.1.2	Term	Cardiac arrhythmias
E.1.2	System Organ Class	10007541 - Cardiac 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 the safety and efficacy of delayed discontinuation of DOAC anticoagulant therapy in patients undergoing oral surgery classified as moderate bleeding risk.

Valutare la sicurezza e l’efficacia della ritardata interruzione della terapia anticoagulante DOACs in pazienti da sottoporre ad interventi di chirurgia orale classificati a moderato rischio emorragico.

E.2.2

Secondary objectives of the trial

Not applicable

Non applicabile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Adult patients of all ages receiving DOACs who have indications for the following outpatient oral surgery and who are attributed a risk of moderate postoperative bleeding:
To multiple dental avulsions of teeth affected by carious and / or periodontal pathology;
B surgical avulsion of teeth in dental inclusion and disodontiasis;
C biopsy samples of the mucous membrane of the oral cavity and of the bone of the maxillary bases for diagnostic purposes;
D excision of inflammatory odontogenic cystic neoformations or from endosseous development;
E Bone Courettage by excision of necrotic bone.

2) Patients able to understand the nature of the study and the treatments, to provide written informed consent and willing to undergo specific pre- and post-operative checks and tests.

1) Pazienti maggiorenni di tutte le età in terapia con DOACs che presentano indicazioni per i seguenti interventi di chirurgia orale ambulatoriale e a cui è attribuito un rischio di sanguinamento moderato post-operatorio:
A avulsioni dentarie multiple di denti affetti da patologia cariosa e/o parodontale;
B avulsione chirurgica di denti in inclusione dentaria e disodontiasi;
C prelievi bioptici della mucosa del cavo orale e dell’osso delle basi mascellari a scopo diagnostico;
D asportazione di neoformazioni cistiche odontogene infiammatorie o da sviluppo endossee;
E Courettage osseo per asportazione di osso necrotico.

2) Pazienti in grado di comprendere la natura dello studio e i trattamenti, di fornire il consenso informato scritto e disponibili a sottoporsi a specifici controlli e test pre- e post-operatori.

E.4

Principal exclusion criteria

Exclusion criteria
1) Patients not taking DOAC.
2) Patients requiring oral surgery who are attributed a low or high risk of postoperative haemorrhage such as simple single extractions or surgical procedures involving bone resections or osteotomies.
3) Patients on anticoagulant treatment who require oral surgery for which cardiologists have expressed a justified request for exclusion.

Criteri di esclusione
1) Pazienti che non assumono DOAC.
2) Pazienti che necessitano di interventi di chirurgia orale a cui è attribuito un rischio basso o alto di emorragia postoperatoria quali le estrazioni singole semplice o interventi chirugici che prevedono resezioni ossee od osteotomie.
3) Pazienti in trattamento anticoagulante che necessitano di interventi di chirurgia orale per i quali i cardiologici abbiano espresso motivata richiesta di esclusione.

E.5 End points

E.5.1

Primary end point(s)

Not applicable

Non applicabile

E.5.1.1

Timepoint(s) of evaluation of this end point

Not applicable

Non applicabile

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

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

Diversa tempistica di sospensione del DOAC

Different timing of suspension of the DOAC

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.8.6 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

All patients will be re-evaluated at a clinical check-up to be carried out one week after surgery. Patients will be subjected to physical examination and questioned about the clinical course.

Tutti i pazienti saranno rivalutati ad un controllo clinico da effettuarsi una settimana dopo l’intervento chirurgico. I pazienti saranno sottoposti ad esame obiettivo e interrogati sul decorso clinico.

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:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

199

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

400

F.4.2

For a multinational trial

F.4.2.1

In the EEA

400

F.4.2.2

In the whole clinical trial

400

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 procedure, patients will be instructed to take a semi-liquid and cold diet for a week, to use external ice for the duration of the surgery day. All patients will be provided with a telephone number to use in case of post-operative bleeding. All patients will be re-evaluated at a clinical check-up to be carried out one week after surgery. Patients will be subjected to physical examination and questioned about the clinical course.

Dopo la procedura, i pazienti saranno istruiti ad assumere dieta semiliquida e fredda per una settimana, ad utilizzare ghiaccio esterno per tutta la durata del giorno dell’intervento. A tutti i pazienti sarà fornito il recapito telefonico da utilizzare in caso di emorragia post-operatoria. Tutti i pazienti saranno rivalutati ad un controllo clinico da effettuarsi una settimana dopo l’intervento chirurgico. I pazienti saranno sottoposti ad esame obiettivo e interrogati sul decorso clinico.

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

2022-11-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-02-08

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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