C15.378
Conditions
Keywords
Febrile neutropenia
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.
Interventions
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC)
DRUGAmoxicillin-clavulanate ciprofloxacin
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C)
Sponsors
Versailles Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apyrexia at day 4 | 4 days | Clinical success, defined as apyrexia measured 4 days after the first antibiotic dose, without modification of antibiotic treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Adequacy of empirical antibiotic treatment to the treatment prescribed at randomization (Hour 48; Day 4; Day 14) | (Hour 48; Day 4; Day 14) | — |
| Treatment compliance (treatment compliance surveillance form Day1 to Day 7) | Day 1 to Day 7 | — |
| Any modification in antibiotic treatment (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) | (Day 14) | — |
| Antibiotic duration (Day 14) | (Day 14) | — |
| Bacteraemia (in the subgroup of secondarily hospitalized patients) (Day 14) | (Day 14) | — |
| Empirical antibiotic treatment inefficient against identified bacteria (in the subgroup of secondarily hospitalized patients) (Day 14) | (Day 14) | — |
| Pseudomonas aeruginosa bacteraemia (Day 14) | (Day 14) | — |
| Evaluation at H48 by phone call (hospitalization, vital status) | Hour 48 | — |
| Evaluation at Day 14 by phone call, review of medical charts and retrospective collection of biological and microbiological data | Day 14 | Hospitalization, vital status, occurrence of the following events: tendinous pain, joint pain, confusion, QT prolongation, cardiac rhythm disorder, allergy, C. difficile colitis |
| Evaluation at Day 30 by phone call (hospitalization, vital status) | Day 30 | — |
Countries
France
Contacts
CONTACTMélody FORT
Outcome results
None listed