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
2 other identifiers
interventional
1,526
1 country
16
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2026
Typical duration for phase_3
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2026
CompletedFirst Submitted
Initial submission to the registry
March 12, 2026
CompletedFirst Posted
Study publicly available on registry
March 19, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2028
March 19, 2026
March 1, 2026
2 years
March 12, 2026
March 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Apyrexia at day 4
Clinical success, defined as apyrexia measured 4 days after the first antibiotic dose, without modification of antibiotic treatment
4 days
Secondary Outcomes (16)
Fever recurrence before Day 14
Day 1 to Day 14; Hour 48; Day 4; Day 14
Hospitalization for treatment failure (Hour 48; Day 4; Day 14; Day 30)
(Hour 48; Day 4; Day 14; Day 30)
Hospitalization in intensive care unit for treatment failure (Hour 48; Day 14; Day 30)
(Hour 48; Day 14; Day 30)
Death (Day 14; Day 30)
(Day 14; Day 30)
Death due to infection (Day 14; Day 30)
(Day 14; Day 30)
- +11 more secondary outcomes
Study Arms (2)
amoxicillin-clavulanate [AC]
EXPERIMENTALOral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC)
amoxicillin-clavulanate and ciprofloxacin [AC + C]
ACTIVE COMPARATOROral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C)
Interventions
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C)
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
CH Jacques Coeur
Bourges, France
CH de BRIVE LA GAILLARDE
Brive-la-Gaillarde, France
CHU Caen-Normandie
Caen, France
CH de Versailles
Le Chesnay, France
CHU d'ORLEANS
Orléans, France
Hopital de La Pitie Salpetriere
Paris, France
Hopital Necker Enfants Malade
Paris, France
Hopital Saint Louis
Paris, France
CH de Perigueux
Périgueux, France
CH Poissy Saint-Germain-en-Laye
Poissy, France
Institut Curie
Saint-Cloud, France
CH de SAINT NAZAIRE
Saint-Nazaire, France
CHU de SAINT-ETIENNE
Saint-Priest-en-Jarez, France
CH de SAUMUR
Saumur, France
CH de Valence
Valence, France
Groupe Hospitalier Haute Saône Vesoul
Vesoul, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 12, 2026
First Posted
March 19, 2026
Study Start
March 1, 2026
Primary Completion (Estimated)
March 1, 2028
Study Completion (Estimated)
September 1, 2028
Last Updated
March 19, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share