PROPHYLOXITIN-Intermittent cefoxitin administration versus loading bolus followed by continuous infusion for the prevention of surgical site infection in colorectal surgery: a multicentre, double-blind, randomized controlled clinical trial

2024-515146-16-00 Protocol PROPHYLOXITIN Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 15 May 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 21 sites · Protocol PROPHYLOXITIN

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 2,000
Countries 1
Sites 21

Colorectal surgery

The main objective is to demonstrate the superiority of a loading dose of cefoxitin followed by continuous infusion over standard of care boluses in reducing SSI within 30 days after colorectal surgery

Key facts

Sponsor
Centre Hospitalier Universitaire De Poitiers
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
Trial duration
15 May 2023 → ongoing
Decision date (initial)
2024-08-20
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
CHU de Poitiers · DGOS FRANCE

External identifiers

EU CT number
2024-515146-16-00
EudraCT number
2022-003262-20
ClinicalTrials.gov
NCT05755789

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Prophylaxis, Efficacy

The main objective is to demonstrate the superiority of a loading dose of cefoxitin followed by continuous infusion over standard of care boluses in reducing SSI within 30 days after colorectal surgery

Secondary objectives 10

  1. Incidence of individual types of SSI
  2. Incidence of surgical reintervention
  3. Incidence of anastomotic leak
  4. Incidence of postoperative complication according to the Dindo and Clavien classification
  5. Incidence of Clostridium difficile infection
  6. Incidence of hospital readmission
  7. Incidence of unexpected admission to the ICU
  8. Duration of hospital stay
  9. Postoperative mortality
  10. Adverse events during the antibiotic administration

Conditions and MedDRA coding

Colorectal surgery

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Randomization
2 arm-intervention/control
 Randomised Controlled Double [{"id":182817,"code":2,"name":"Investigator"},{"id":182816,"code":1,"name":"Subject"}] Intervention: innovative administration scheme for surgical antibiotic prophylaxis: loading bolus of cefoxitin [2g] followed by continuous infusion of cefoxitin [0.5g/h] plus additional boluses of placebo every 2 hours until the end of surgical closure)
Control: recommended administration scheme: loading bolus of cefoxitin [2g] followed by additional bolus of cefoxitin [1g] every 2 hours plus continuous infusion of placebo until the end of surgical closure).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Adult patients (≥18 years)
  2. Undergoing colorectal surgery (predictable duration > 90 min)
  3. Patients benefiting from a Social Security system or benefiting from it through a third party
  4. Free subject, without guardianship or curatorship or subordination
  5. Having given their informed consent

Exclusion criteria 8

  1. Patients with known history of hypersensitivity to cefoxitin or others beta-lactams
  2. Patients with extreme severe obesity (defined by a body mass index greater than 50 kg/m2)
  3. Patients with severe renal insufficiency (clearance creatinine < 30ml/min)
  4. Active bacterial infection at the time of surgery or recent antimicrobial therapy (up to 2 weeks before surgery) except for oral surgical antibiotic prophylaxis
  5. Participation to another clinical trial aimed at reducing SSI
  6. Patients already previously enrolled in this study
  7. Pregnant or breastfeeding women, women of childbearing age who do not have effective contraception (hormonal/mechanical: per os, injectable, transcutaneous, implantable, intrauterine device, or surgical: tubal ligation, hysterectomy, total ovariectomy)
  8. Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, adults under legal protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Proportion of patients with any SSI within 30 days after surgery.

Secondary endpoints 10

  1. Proportion of patients with each type of SSI (superficial, deep and/or organ–space infection)
  2. Proportion of patients with surgical reintervention
  3. Proportion of patients with anastomotic leak
  4. Proportion of patients with postoperative complication according to the Dindo and Clavien classification
  5. Proportion of patients with Clostridium difficile infection
  6. Hospital readmission censored at day 30
  7. Unexpected admission to the ICU censored at day 30
  8. Duration of hospital stay and hospital free days
  9. All-causes mortality
  10. Proportion of per operative adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

CEFOXITINE PANPHARMA 1 g, poudre pour solution injectable (IV)

PRD5536666 · Product

Active substance
Cefoxitin Sodium
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
4 g gram(s)
Max total dose
4 g gram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
J01DA05 — CEFOXITIN
Marketing authorisation
34009 561 281 9 8
MA holder
PANPHARMA
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

CHLORURE DE SODIUM 0,9 % AGUETTANT, solution pour perfusion

PRD10486861 · Product

Active substance
Sodium Chloride
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
100 ml millilitre(s)
Max total dose
100 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B05XA03 — SODIUM CHLORIDE
Marketing authorisation
34009 352 292 8 1
MA holder
LABORATOIRE AGUETTANT
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Poitiers

8 Total trials 5 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Centre Hospitalier Universitaire De Poitiers
Address
2 Rue De La Miletrie
City
Poitiers
Postcode
86000
Country
France

Scientific contact point

Organisation
Centre Hospitalier Universitaire De Poitiers
Contact name
Pr Matthieu BOISSON

Public contact point

Organisation
Centre Hospitalier Universitaire De Poitiers
Contact name
Pr Matthieu BOISSON

Locations

1 EU/EEA country · 21 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruiting 2,000 21
Rest of world — 0 —

Investigational sites

France

21 sites · Ongoing, recruiting
Centre Hospitalier Universitaire D'Angers
Anesthésie Réanimation, 4 Rue Larrey, 49100, Angers
Centre Hospitalier Universitaire De Poitiers
Service d'Anesthésie-Réanimation et Médecine Péri-Opératoire, 2 Rue De La Miletrie, 86000, Poitiers
Centre Leon Berard
Anesthésie-Réanimation, 28 Rue Laennec, 69008, Lyon
Institut Paoli Calmettes
Unité Fonctionnelle d'Anesthésie, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
Les Hopitaux Universitaires De Strasbourg
Réanimation Chirurgicale Polyvalente, 1 Place De L Hopital, Cs 80426, Strasbourg Cedex
Centre Hospitalier Universitaire Grenoble Alpes
Anesthésie et Réanimation, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
Centre Hospitalier Bretagne Atlantique
Réanimation Polyvalente, 20 Boulevard General Maurice Guillaudot, 56000, Vannes
Centre Hospitalier Universitaire De Toulouse
Anesthésie Réanimation, 2 Rue Viguerie, 31300, Toulouse
Groupe Hospitalier Bretagne Sud
Anesthésie-Réanimation, 5 Avenue Etienne Francois De Choiseul, 56100, Lorient
Assistance Publique Hopitaux De Paris
Anesthésie-Réanimation, 20 Rue Leblanc, 75015, Paris
University Hospital Of Clermont-Ferrand
Anesthésie, Réanimation et Médecine Périopératoire, 58 Rue Montalembert, 63003, Clermont Ferrand Cedex 1
CHRU De Nancy
Anesthésie-Réanimation, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
Hopital Prive Sevigne
Anesthésie-Réanimation, 3 Rue Du Chene Germain, 35510, Cesson Sevigne
Hospices Civils De Lyon
Anesthésie, 3 Quai Des Celestins, Bp 2251, Lyon Cedex 02
Centre Hospitalier Universitaire De Caen Normandie
Anesthésie Réanimation, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Centre Hospitalier Universitaire De Saint Etienne
Anesthésie-Réanimation, 25 Boulevard Pasteur, 42100, Saint-Etienne
Centre Hospitalier De Saint-Brieuc
Anesthésie, 10 Rue Marcel Proust, 22000, Saint-Brieuc
Centre Hospitalier Universitaire De Nantes
Anesthésie Réanimation, 5 Allee De L Ile Gloriette, Cs 69301, Nantes Cedex 1
Centre Hospitalier De Pau
Anesthésie, 4 Boulevard Hauterive, 64000, Pau
Clinique Pasteur
Anesthésie-Réanimation, 45 Avenue De Lombez, Cs 27617, Toulouse Cedex 3
Hôpital Privé Arras Les Bonnettes
Anesthésie-Réanimation, 2 rue du Dr Forgeois, 62000, ARRAS

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2023-05-15 2023-06-22

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-515146-16-00_PROPHYLOXITIN 15
Protocol (for publication) D1_Protocole_V10_20240301_2024-515146-16-00_PROPHYLOXITIN 10
Protocol (for publication) D1_Protocole_V9_20240226_2024-515146-16-00_PROPHYLOXITIN 9
Recruitment arrangements (for publication) K1_RecruitementArrangement_2024-515146-16-00_PROPHYLOXITIN 1
Recruitment arrangements (for publication) K1_Recruitment Arrangements_2024-515146-16-00_PROPHYLOXITIN 1
Subject information and informed consent form (for publication) L1_SIS_2024-515146-16-00_PROPHYLOXITIN 5
Subject information and informed consent form (for publication) L1_SIS_Addendum_2024-515146-16-00_PROPHYLOXITIN 1
Subject information and informed consent form (for publication) L1_SIS_ICF_V4_231228_2024-515146-16-00_PROPHYLOXITIN 4
Subject information and informed consent form (for publication) L1_SIS_LCF_2024-515146-16-00_PROPHYLOXITIN 7
Subject information and informed consent form (for publication) L1-SIS_Addendum_2024-515146-16-00_PROPHYLOXITIN 1
Subject information and informed consent form (for publication) L2-Affiche_2024-515146-16-00_PROPHYLOXITIN 1
Subject information and informed consent form (for publication) L2-Flyer_2024-515146-16-00_PROPHYLOXITIN 2
Summary of Product Characteristics (SmPC) (for publication) E2_SMPC_Cefoxitin_20220613_2024-515146-16-00_PROPHYLOXITIN NA
Summary of Product Characteristics (SmPC) (for publication) E2_SMPC_NaCl_2024-515146-16-00_PROPHYLOXITIN NK
Synopsis of the protocol (for publication) D1_Synopsis_Protocol_2024-515146-16-00_PROPHYLOXITIN 7
Synopsis of the protocol (for publication) D1_Synopsis_Protocol_2024-515146-16-00_PROPHYLOXITIN 6
Synopsis of the protocol (for publication) D1_SynopsisProtocol_V4_20231228_2024-515146-16-00_PROPHYLOXITIN 4

Application history

5 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-07-22 France Acceptable
2024-08-14
 2024-08-20
2 SUBSTANTIAL MODIFICATION SM-1 2025-01-21 France Acceptable
2025-04-06
 2025-04-07
3 NON SUBSTANTIAL MODIFICATION NSM-6 2025-05-06 France Acceptable
2025-04-06
 2025-05-06
4 SUBSTANTIAL MODIFICATION SM-2 2025-11-25 France Acceptable
2025-12-12
 2026-01-23
5 NON SUBSTANTIAL MODIFICATION NSM-7 2026-04-23 France Acceptable
2025-12-12
 2026-04-23

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