Clinical Trials Register

Summary
EudraCT Number:	2017-000334-59
Sponsor's Protocol Code Number:	PI2017_843_0002
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2018-01-22
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2017-000334-59

A.3

Full title of the trial

The value of post-operative antibiotic therapy after laparoscopic appendectomy for complicated acute appendicitis (other than for generalized peritonitis): a prospective, randomized, placebo-controlled Phase III study.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

ABAP

A.4.1

Sponsor's protocol code number

PI2017_843_0002

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	CHU Amiens-Picardie
B.1.3.4	Country	France
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	DGOS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CHU Amiens-Picardie
B.5.2	Functional name of contact point	CRA
B.5.3	Address:
B.5.3.1	Street Address	CHU Amiens-Picardie
B.5.3.2	Town/ city	Amiens
B.5.3.3	Post code	80054
B.5.3.4	Country	France
B.5.4	Telephone number	33322 08 83 69
B.5.5	Fax number	33322 08 96 45
B.5.6	E-mail	boussault.annabelle@chu-amiens.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	ceftriaxone mylan 2g, poudre pour solution injectable
D.2.1.1.2	Name of the Marketing Authorisation holder	MYLAN SAS
D.2.1.2	Country which granted the Marketing Authorisation	France
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	CEFTRIAXONE
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	LEVOFLOXACINE KABI 5 MG/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	fresenius kabi France
D.2.1.2	Country which granted the Marketing Authorisation	France
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	levofloxacine kabi 5MG/Ml
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.IMP: 3
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	METRONIDAZOLBBRAUN
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratoire B BRAUN MEDICAL
D.2.1.2	Country which granted the Marketing Authorisation	France
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	METRONIDAZOL
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

E.1.1.1

Medical condition in easily understood language

The value of post-operative antibiotic therapy after laparoscopic appendectomy for complicated acute appendicitis (other than for generalized peritonitis)

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to evaluate the impact of the absence of post-operative antibiotic therapy on the organ space surgical site infection (SSI) rate in patients presenting with CAA (other than in cases of generalized peritonitis).

E.2.2

Secondary objectives of the trial

The secondary objectives are:
1. patient-related:
• post-operative quality of life, since the latter can be impaired by complications related to the antibiotic treatment itself (colitis) or the absence of antibiotics (abscesses).
2. infection-related:
• the impact of post-operative antibiotic therapy on the proportion of patients with superficial SSIs at POD30.
• the overall post-operative infection rate at POD30.
• the number of antibiotic-free days during the first 30 days post-surgery.
• description of the microbial flora.
• the balance between antibiotic therapy and microbial resistance.
3. surgery-related:
• post-operative morbidity and mortality, according to the Dindo-Clavien classification and the CCI.
• the LOS.
• the rehospitalization rate.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Related to the disease:
• CAA suspected pre-operatively through a Saint-Antoine score ≤3 and confirmed peroperatively by the presence of a perforated appendicitis, extraluminal fecaliths, abscesses and/or localized peritonitis (pus in one or two abdominal quadrants).
• Laparoscopic appendectomy.
Related to the research:
• Aged 18 or over
• Provision of written, informed consent

E.4

Principal exclusion criteria

• Related to the diagnosis: other diseases (Crohn’s disease, ulcerative colitis, treatment with an immunosuppressive therapy).
• Related to the severity of the appendicitis:
• A Saint-Antoine score of 4 or 5 (non-complicated acute appendicitis)
• Severe sepsis, septic shock, generalized peritonitis
• Related to the treatment:
o A decision to perform open appendectomy.
o Patients who received an adaptive dose of Levofloxacine 250 mg/24H instead of 500 mg/24H in pre-operative or in per-operative
o allergy to metronidazole or to one of the excipient
o Contra-indication to the use of ceftriaxone (hypersensibility to the active substance, to another cephalosporin, to the excipient of the used speciality), history of severe hypersesibility (as anaphylactic shock), history of hypersensibility to another antibiotic of the beta-lactamin family (penicillin, monobactam, carbapénèmes)
o Contra-indication to the use of levofloxacin, hypersensibility to levofloxacin, to another quinolone or to the excipient of one of the use speciality, hypersensibility to levofloxacine ou any other quinolone or to any excipient, epilepsia, history of tendinitis when injection of fluoroquinolones.
• Related to the patient
o Living at more than one hour from an hospital

E.5 End points

E.5.1

Primary end point(s)

The primary outcome is the proportion of patients with deep SSIs by POD30. Deep SSIs are officially defined by the CDC as infections that occur within 30 days of surgery AND appear to be related to the surgery AND affect the organ or the cavity around the surgical site (i.e. any anatomical structure – other than the incision – that is opened or handled during surgery) AND for which at least one of the following signs is observed: pus coming from a drain placed in the organ or cavity; germs isolated from a liquid or tissue sample collected aseptically from the organ or cavity; an abscess or another obvious sign of infection of the organ or cavity found by macroscopic examination during subsequent surgery or in a radiological or histopathological examination. Infection of the organ or cavity is diagnosed by the surgeon (or the physician attending to the patient). In the protocol, the SSI will be confirmed on a CT scan by the presence of a deep abscess (defined as a fluid collection with cavity walls and gases within a fluid collection), which will be treated with antibiotics (either alone or in combination with radiological or surgical drainage, depending on the clinician’s decision).
The investigators evaluating the primary endpoint will be blinded to the treatment group.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 30

E.5.2

Secondary end point(s)

1. Patient-related
• Quality of life prior to surgery, on discharge and on POD30, using the EuroQoL 5D and SF36 questionnaires.
2. Infection-related
• The proportion of patients with superficial SSIs, defined as infections that occur within 30 days of the intervention AND affect the skin and subcutaneous tissue AND or which at least one of the following signs is observed: pus coming from the superficial part of the incision, germs isolated from a liquid or tissue sample collected aseptically from the superficial part of the incision, a sign of infection (pain, tenderness, redness, burning, etc.) associated with deliberate opening of the superficial part of the incision by the surgeon (except if the culture is negative). Infection of the superficial part of the incision is diagnosed by the surgeon (or the physician attending to the patient).
• The post-operative infection rates by POD30, including SSIs and remote infections.
• The number of antibiotic-free days between randomization and POD30.
• The description of the microbial flora, as found in the antibiogram of the per-operative sample that is collected in all cases.
• The balance between antibiotic therapy and microbial resistance. The antibiotic treatment will be considered to be adequate if no germs are found in the per-operative sample or if all of the detected germs are sensitive to the administered antibiotic therapy. The antibiotic treatment will be considered to be inadequate if the per-operative sample is positive for resistant germs.
3. Surgery-related
• Morbidity and mortality according to the Dindo-Clavien classification and the CCI, Slankamenac, Ann Surg, 2014; 260:757-62).
• LOS, defined as the number of days of hospitalization between surgery and discharge.
• The rehospitalization rate, defined as rehospitalization during the study period.

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 30

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

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

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

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

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

E.8.7

Trial has a data monitoring committee

Yes

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	No
F.1.2.1	Number of subjects for this age range:	1294
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	200
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	1494

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

2018-03-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-06-05

P. End of Trial
P.	End of Trial Status	Trial now transitioned

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials