C15.378Phase 3AC-CIFNCT07483736
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.
A Phase 3 study testing amoxicillin-clavulanate and Amoxicillin-clavulanate ciprofloxacin in people with C15.378, run by Versailles Hospital at 16 sites in France.
Trial summary
The combination of amoxicillin-clavulanate (AC) and a fluoroquinolone (FQ) is currently recommended for the treatment for outpatients with hematologic malignancies presenting with chemotherapy-induced fever (CIF), if the expected duration of neutropenia is < 7 days. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- C15.378
- What is being tested?
- amoxicillin-clavulanate and Amoxicillin-clavulanate ciprofloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,526 participants
- Where
- 16 sitesFrance
- Study dates
- Mar 2026to Sep 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- Written informed consent
- 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))
- Affiliated to or beneficiary of the welfare care
Who cannot join
- 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:
- 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),
- treatment with tizanidine,
- previous hypersensitivity to any quinolone,
- previous tendonitis attributed to any fluoroquinolone,
- 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
Trial locations and contacts
16 sites in 1 country. Contact the study team or a site near you to ask about taking part.
16 sites in 1 country
France16 sites
CH Jacques Coeur
Bourges
Dr BOURREAU, +33248487294, anna.bourreau@ch-bourges.fr
CH de BRIVE LA GAILLARDE
Brive-la-Gaillarde
Dr VILLESUZANE, +3355592651, camille.villesuzanne@ch-brive.fr
CHU Caen-Normandie
Caen
Dr DELAPIERRE, +33231272124, delapierre-b@chu-caen.fr
CH de Versailles
Le Chesnay
Pr ROUSSELOT, +33139638909, phrousselot@ght78sud.fr
CHU d'ORLEANS
Orléans
Dr OCHMANN, +33238514210, marlene.ochmann@chr-orleans.fr
Hopital de La Pitie Salpetriere
Paris
Dr BOUSSEN, +33142162834, ines.boussen@aphp.fr
Hopital Necker Enfants Malade
Paris
Dr SUAREZ, +33144495368, felipe.suarez@aphp.fr
Hopital Saint Louis
Paris
Dr RAFFOUX, +33142499649, emmanuel.raffoux@aphp.fr
CH de Perigueux
Périgueux
Dr CALMETTES, +33553452585, claire.calmettes@ch-perigueux.fr
CH Poissy Saint-Germain-en-Laye
Poissy
Dr FLATEAU, +33139274645, clara.flateau@ght-yvelinesnord.fr
Institut Curie
Saint-Cloud
DR ELLOUZ, +33147111680, cyrine.ellouz@curie.fr
CH de SAINT NAZAIRE
Saint-Nazaire
Dr LESTANG, +33272278000, e.lestang@ch-saintnazaire.fr
CHU de SAINT-ETIENNE
Saint-Priest-en-Jarez
Dr CORNILLON, +33477822856, jerome.cornillon@chu-st-etienne.fr
CH de SAUMUR
Saumur
Dr TRUCHAN, +33241533544, matruchan@gmail.com
CH de Valence
Valence
Dr ROBERT, +33475755769, philippine.robert@ch-valence.fr
Groupe Hospitalier Haute Saône Vesoul
Vesoul
Dr FAURE, +3384966579, c.faure@gh70.fr
About this study
Official title: 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
The combination of amoxicillin-clavulanate (AC) and a fluoroquinolone (FQ) is currently recommended for the treatment for outpatients with hematologic malignancies presenting with chemotherapy-induced fever (CIF), if the expected duration of neutropenia is < 7 days. However, infections due to Pseudomonas aeruginosa (naturally resistant to AC) are rare in this population. Furthermore, FQ might result in severe adverse events, and to the selection of bacterial resistance.
The investigators hypothesize that monotherapy with AC is non-inferior to the reference treatment AC + FQ in the outpatient treatment of CIF in adult hematology patients.
Method: Pragmatic, multicentre, randomized clinical trial, controlled in two parallel groups, with stratified randomization according to the type of haematological disorder. The study will include 1,526 adult patients with one of the following haematological disorders: (1) lymphoma of all histology types treated with the goal of remission; (2) myelodysplasia treated with azacytidine; (3) acute myeloblastic leukemia receiving non-intensive care, with a basal neutrophils count > 1000/mm3. The participants will be randomized prior to chemotherapy to receive either Amoxicillin-clavulanate 1g/152 mg tid. (AC) or Amoxicillin-clavulanate 1g/152 mg tid. and Ciprofloxacin 500 mg bid. (AC+C) orally for 7 days, to be taken in case of CIF. Only the first episode of CIF of each patient will be included in the analysis. The main evaluation criterion will be clinical success, defined as apyrexia 4 days after the first antibiotic dose, without modification of antibiotic treatment. The main secondary evaluation criteria (recorded at Day 14) will be fever recurrence, hospital admission, modification of antibiotic treatment, treatment with a beta-lactamine antibiotic efficient against P. aeruginosa, duration of antibiotic treatment, bacteraemia, inefficiency of the study treatment against the identified bacteria, and adverse events of FQ.
- Conditions
- C15.378
- Being tested
- amoxicillin-clavulanate, Amoxicillin-clavulanate ciprofloxacin
- Keywords
- Febrile neutropenia
- Medical subject headings
- Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
amoxicillin-clavulanateDrug
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC)
Amoxicillin-clavulanate ciprofloxacinDrug
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C)
| Study group | Role | What they receive |
|---|---|---|
| amoxicillin-clavulanate [AC] | Experimental | Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC) Receives: Drug: amoxicillin-clavulanate |
| amoxicillin-clavulanate and ciprofloxacin [AC + C] | Active comparator | Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C) Receives: Drug: Amoxicillin-clavulanate ciprofloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apyrexia at day 4
Clinical success, defined as apyrexia measured 4 days after the first antibiotic dose, without modification of antibiotic treatment
Measured: 4 days
Secondary outcomes (16)
Fever recurrence before Day 14
Measured: Day 1 to Day 14; Hour 48; Day 4; Day 14
Hospitalization for treatment failure (Hour 48; Day 4; Day 14; Day 30)
Measured: (Hour 48; Day 4; Day 14; Day 30)
Hospitalization in intensive care unit for treatment failure (Hour 48; Day 14; Day 30)
Measured: (Hour 48; Day 14; Day 30)
Death (Day 14; Day 30)
Measured: (Day 14; Day 30)
Death due to infection (Day 14; Day 30)
Measured: (Day 14; Day 30)
Adequacy of empirical antibiotic treatment to the treatment prescribed at randomization (Hour 48; Day 4; Day 14)
Measured: (Hour 48; Day 4; Day 14)
Treatment compliance (treatment compliance surveillance form Day1 to Day 7)
Measured: Day 1 to Day 7
Any modification in antibiotic treatment (Hour 48; Day 4; Day 14)
Measured: (Hour 48; Day 4; Day 14)
Treatment with a beta-lactam antibiotic with efficacy against P. aeruginosa (Day 14)
Measured: (Day 14)
Antibiotic duration (Day 14)
Measured: (Day 14)
Bacteraemia (in the subgroup of secondarily hospitalized patients) (Day 14)
Measured: (Day 14)
Empirical antibiotic treatment inefficient against identified bacteria (in the subgroup of secondarily hospitalized patients) (Day 14)
Measured: (Day 14)
Pseudomonas aeruginosa bacteraemia (Day 14)
Measured: (Day 14)
Evaluation at H48 by phone call (hospitalization, vital status)
Measured: Hour 48
Evaluation 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
Measured: Day 14
Evaluation at Day 30 by phone call (hospitalization, vital status)
Measured: Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study startMar 2026 (estimated)
- Primary completionMar 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for C15.378Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,526 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Versailles Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Clara FLATEAU, Poissy-Saint Germain Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07483736
- Sponsor's protocol ID
- P23/12 - AC-CIF
- Other IDs
- 2025-520995-24-00, 2025
- Acronym
- AC-CIF
- Status last verified
- Mar 2026
- First submitted
- 12 Mar 2026
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No