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)

March 17, 2026 updated by: Clara FLATEAU, Versailles Hospital

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1526

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  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. 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))
  4. Affiliated to or beneficiary of the welfare care

Exclusion Criteria:

  • 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:

    1. 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),
    2. treatment with tizanidine,
    3. previous hypersensitivity to any quinolone,
    4. previous tendonitis attributed to any fluoroquinolone,
    5. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: amoxicillin-clavulanate [AC]
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC)
Drug: amoxicillin-clavulanate
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC)
Active Comparator: amoxicillin-clavulanate and ciprofloxacin [AC + C]
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C)
Drug: Amoxicillin-clavulanate ciprofloxacin
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Apyrexia at day 4
Time Frame: 4 days
Clinical success, defined as apyrexia measured 4 days after the first antibiotic dose, without modification of antibiotic treatment
4 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fever recurrence before Day 14
Time Frame: Day 1 to Day 14; Hour 48; Day 4; 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)
Time Frame: (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)
Time Frame: (Hour 48; Day 14; Day 30)
(Hour 48; Day 14; Day 30)
Death (Day 14; Day 30)
Time Frame: (Day 14; Day 30)
(Day 14; Day 30)
Death due to infection (Day 14; Day 30)
Time Frame: (Day 14; Day 30)
(Day 14; Day 30)
Adequacy of empirical antibiotic treatment to the treatment prescribed at randomization (Hour 48; Day 4; Day 14)
Time Frame: (Hour 48; Day 4; Day 14)
(Hour 48; Day 4; Day 14)
Treatment compliance (treatment compliance surveillance form Day1 to Day 7)
Time Frame: Day 1 to Day 7
Day 1 to Day 7
Any modification in antibiotic treatment (Hour 48; Day 4; Day 14)
Time Frame: (Hour 48; Day 4; Day 14)
(Hour 48; Day 4; Day 14)
Treatment with a beta-lactam antibiotic with efficacy against P. aeruginosa (Day 14)
Time Frame: (Day 14)
(Day 14)
Antibiotic duration (Day 14)
Time Frame: (Day 14)
(Day 14)
Bacteraemia (in the subgroup of secondarily hospitalized patients) (Day 14)
Time Frame: (Day 14)
(Day 14)
Empirical antibiotic treatment inefficient against identified bacteria (in the subgroup of secondarily hospitalized patients) (Day 14)
Time Frame: (Day 14)
(Day 14)
Pseudomonas aeruginosa bacteraemia (Day 14)
Time Frame: (Day 14)
(Day 14)
Evaluation at H48 by phone call (hospitalization, vital status)
Time Frame: Hour 48
Hour 48
Evaluation at Day 14 by phone call, review of medical charts and retrospective collection of biological and microbiological data
Time Frame: Day 14

Hospitalization, vital status, occurrence of the following events:

tendinous pain, joint pain, confusion, QT prolongation, cardiac rhythm disorder, allergy, C. difficile colitis
Day 14
Evaluation at Day 30 by phone call (hospitalization, vital status)
Time Frame: Day 30
Day 30

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Versailles Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

September 1, 2028

Study Registration Dates

First Submitted

March 12, 2026

First Submitted That Met QC Criteria

March 17, 2026

First Posted (Actual)

March 19, 2026

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 17, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P23/12 - AC-CIF
  • 2025-520995-24-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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