Efficacy of an empirical treatment with Amoxicillin-clavulanate (AC) compared to the combination Amoxicillin-clavulanate and Ciprofloxacin (AC+C) in the outpatient care of chemotherapy-induced fever in adult haematology patients. AC-CIF Protocol

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier De Versailles

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Bacterial Infections and Mycoses [C01]

Decision date (initial)

2025-08-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To demonstrate the non-inferiority of amoxicillin-clavulanate (AC) compared to the reference combination treatment amoxicillin-clavulanate and ciprofloxacin (AC+C), in the empirical oral outpatient treatment of a first episode of CIF in adult haematology patients.

Secondary objectives 7

1. To evaluate and compare between randomized arms: Adherence to the study treatment
2. To evaluate and compare between randomized arms: Incidence of the following negative events: change in antibiotic treatment, relapse, hospitalization, hospitalization in intensive care unit, death
3. To evaluate and compare between randomized arms: Treatment efficacy in the subgroup of neutropenic patients (neutrophils < 500/mm3)
4. To evaluate and compare between randomized arms: Safety of treatment
5. To evaluate and compare between randomized arms: Incidence of bacteraemia (in the subgroup of secondarily hospitalized patients)
6. To evaluate and compare between randomized arms: Incidence of empiric treatment inefficient against identified bacteria (in the subgroup of secondarily hospitalized patients)
7. To identify prognostic factors

Conditions and MedDRA coding

Adult patients treated for haematological disorders, in whom chemotherapy regimens are expected to induce neutropenia lasting <7 days

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. • Adult patients (≥ 18 years) with one of the following haematological disorders (in whom chemotherapy regimens are expected to provoke neutropenia lasting <7 days) (1) lymphoma of all histological types treated with the goal of remission; (2) myelodysplasia treated with azacytidine; (3) acute myeloblastic leukaemia, treated with a non-intensive scheme (azacytidine, azacytidine+venetoclax, other oral treatment against molecular targets)
2. • Written informed consent
3. • Affiliated to or beneficiary of the welfare care
4. • Patient able to understand all information related to the study and able to follow the protocol procedures (phone call and completion of the patient follow-up form (electronic or paper))

Exclusion criteria 21

1. Patient under legal protection
2. Patient deprived of liberty by judicial or administrative decision
3. Patient who is the investigator, any member of the study team, or a relative directly involved in the trial, including assistant physicians, pharmacists, study coordinators, etc…
4. Participation in another interventional clinical trial
5. Impossible collection of informed consent (including non-francophone patient, or cognitive disorders)
6. Body mass index (BMI) > 30
7. Basal neutrophils count < 1000/mm3 (on the latest available blood test performed < 1 month before inclusion)
8. Aminotransferase serum levels > 5 X normal values (on the latest available blood test performed < 1 month before inclusion)
9. Creatinine clearance < 30 mL/min (on the latest available blood test performed < 1 month before inclusion)
10. Previous treatment with CAR-T cells
11. Previous allogeneic or autogeneic bone-marrow transplantation
12. Chronic obstructive pulmonary disease (COPD)
13. Previous invasive fungal infection
14. Allergy to one of the study medications
15. Contraindication to fluoroquinolones: a) hypersensitivity to ciprofloxacin, to other quinolones, or to any of the following excipients (microcrystalline cellulose, crospovidone, anhydrous colloidal silica, magnesium stearate, hypromellose, macrogol, titanium dioxide), b) treatment with tizanidine, c) previous hypersensitivity to any quinolone, d) previous tendonitis attributed to any fluoroquinolone, e) epilepsy
16. Contraindication to amoxicillin-clavulanate
17. QT prolongation (defined as a QT interval > 0.45 seconds for males and > 0.47 seconds for females)
18. Antibiotic prophylaxis (with the exception of the combination sulfamethoxazole and trimethoprim)
19. Pregnant or breastfeeding women
20. Women not using contraception
21. Patient treated with anti-psychotic drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical success, defined as apyrexia measured 4 days after the first antibiotic dose, without modification of antibiotic treatment

Secondary endpoints 4

1. Clinical criteria: a) Fever recurrence before Day 14 (fever surveillance form Day 1 to Day 14; H48; Day 4; Day 14); b) Hospitalization for treatment failure (H48; Day 4; Day 14, Day 30); c) Hospitalization in intensive care unit for treatment failure (H48; Day 14, Day30); d) Death (Day 14, Day 30) e) Death due to infection (Day 14, Day 30)
2. Therapeutic criteria: a) Adequacy of empirical antibiotic treatment to the treatment prescribed at randomization (H48; Day 4; Day 14) b) Treatment compliance (treatment compliance surveillance form Day1 to Day 7) c) Any modification in antibiotic treatment (H48; Day 4; Day 14) d) Treatment with a beta-lactam antibiotic with efficacy against P. aeruginosa (Day 14) e) Antibiotic duration (Day 14)
3. Microbiological criteria: a) Bacteraemia (in the subgroup of secondarily hospitalized patients) (Day 14) b) Empirical antibiotic treatment inefficient against identified bacteria (in the subgroup of secondarily hospitalized patients) (Day 14) c) Pseudomonas aeruginosa bacteraemia (Day 14)
4. Adverses Events: AE and SAE will be collected at every follow-up visit. Eval at H48 by phone call (hospitalization, vital status). Eval at Day 14 by phone call, review of medical charts and retrospective collection of biological and microbiological data (hospitalization, vital status, occurrence of the following events: tendinous pain, joint pain, confusion, QT prolongation, cardiac rhythm disorder, allergy, C. difficile colitis). Eval at Day 30 by phone call (hospit + vital status)

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier De Versailles

Sponsor organisation

Centre Hospitalier De Versailles

Address

177 Rue De Versailles, Le Chesnay Le Chesnay

City

Le Chesnay Rocquencourt

Postcode

78150

Country

France

Scientific contact point

Organisation

Centre Hospitalier De Versailles

Contact name

Dr Clara Flateau

Public contact point

Organisation

Centre Hospitalier De Versailles

Contact name

Mélody FORT

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 files

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

Application history

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