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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
1,526
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. (AC)
Oral treatment, for 7 days duration, with amoxicillin-clavulanate 1g/125 mg tid. and ciprofloxacin 500 mg bid. (AC+C)
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
...and 6 more locations
Apyrexia at day 4
Clinical success, defined as apyrexia measured 4 days after the first antibiotic dose, without modification of antibiotic treatment
Time frame: 4 days
Fever recurrence before Day 14
Time frame: 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)
Hospitalization in intensive care unit for treatment failure (Hour 48; Day 14; Day 30)
Time frame: (Hour 48; Day 14; Day 30)
Death (Day 14; Day 30)
Time frame: (Day 14; Day 30)
Death due to infection (Day 14; Day 30)
Time frame: (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)
Treatment compliance (treatment compliance surveillance form Day1 to Day 7)
Time frame: Day 1 to Day 7
Any modification in antibiotic treatment (Hour 48; Day 4; Day 14)
Time frame: (Hour 48; Day 4; Day 14)
Treatment with a beta-lactam antibiotic with efficacy against P. aeruginosa (Day 14)
Time frame: (Day 14)
Antibiotic duration (Day 14)
Time frame: (Day 14)
Bacteraemia (in the subgroup of secondarily hospitalized patients) (Day 14)
Time frame: (Day 14)
Empirical antibiotic treatment inefficient against identified bacteria (in the subgroup of secondarily hospitalized patients) (Day 14)
Time frame: (Day 14)
Pseudomonas aeruginosa bacteraemia (Day 14)
Time frame: (Day 14)
Evaluation at H48 by phone call (hospitalization, vital status)
Time frame: 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
Time frame: Day 14
Evaluation at Day 30 by phone call (hospitalization, vital status)
Time frame: Day 30
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