Amoxicillin-clavulanate Alone or in Combination With Ciprofloxacin in Low-Risk Febrile Neutropenic Adult Patients: A Prospective, Double-blind, Randomized, Non-Inferiority Multicenter, Phase III Clinical Trial.

Phase 3

Withdrawn

• Conditions: Febrile Neutropenia
• Interventions: Drug: Amoxicillin Clavulanate; Drug: Placebo; Drug: Ciprofloxacin

• Registration Number: NCT04698057
• Lead Sponsor: Poitiers University Hospital

Brief Summary

In low risk neutropenic fever in cancer, standard of care is the association of amoxicillin clavulanate and ciprofloxacin. But in this population, the rate of fever related to infection is very low, leading to a overtreatment of the patients. The aim of this study is to validate a descalation of the antibiotherapy with safety concerns.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-04
• Study First Submitted QC: 2021-01-05
• Study First Posted: 2021-01-06
• Status Verified: 2022-03
• Study Start: 2022-03-01
• Last Update Submitted: 2022-03-16
• Last Update Posted: 2022-03-31
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Patient ≥ 18 years old
• Treated for a solid cancer or a hematological malignancy
• Presented with low-risk* febrile neutropenia due to chemotherapy with an expected duration of neutropenia ≤ 7 days
• Neutropenia is defined by an absolute neutrophil count ≤ 500/mm3.
• Fever is defined by temperature ≥ 38.3° or ≥ 38° twice during a 1-hour interval.
• Signing informed consent *Low risk is defined by MASCC score ≥ 21

Exclusion Criteria

• Hypersensitivity to the active substances: amoxicillin-clavulanic, ciprofloxacin, penicillins, to other quinolones or to one of the excipient
• History of severe immediate hypersensitivity reaction to another beta-lactam
• History of jaunditis/hepatic impairment related to amoxicillin/clavulanic
• Concomitant administration of ciprofloxacin and tizanidine.
• Clinical signs of focal infection including history of untreated dental abscess.
• Signs of sepsis or organ failure.
• Severe immune deficiency other than the current cancer, except controlled-HIV infection
• Gastrointestinal symptoms requiring intravenous treatment (mucositis, vomiting, severe diarrhea...).
• Known aminotransferase serum levels > 5 x normal values.
• Known renal insufficiency defined as creatinine clearance of < 30 mL/min (MDRD).
• Antibiotherapy within 24h before enrollment. Prophylactic use of amoxicillin is an exclusion criterium whereas prophylactic use of trimethoprim-sulfamethoxazole (cotrimoxazole) and penicillin G (Oracilline®) are not and will be considered in the analysis.
• History of infection or colonization due to bacteria resistant to experimental drugs in the previous year
• Can be enrolled in the study only once.
• Patients not benefiting from a Social Security scheme or not benefiting from it through a third party.
• Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social institution, adults under legal protection, and finally patients in emergencies
• Pregnant or breastfeeding women, women at age to procreate and not using effective contraception (either hormonal / mechanical : oral, injection, subcutaneous, implantable, intrauterine device, or surgical : tubal ligation, hysterectomy, total ovariectomy).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amoxicillin clavulanate + ciprofloxacin	Amoxicillin Clavulanate	Treatment with amoxicillin-clavulanate 1g tib and ciprofloxacine 750mg bid for 5 days
Amoxicillin clavulanate + Placebo	Placebo	Treatment with amoxicillin-clavulanate 1g tib for 5 days
Amoxicillin clavulanate + Placebo	Amoxicillin Clavulanate	Treatment with amoxicillin-clavulanate 1g tib for 5 days
Amoxicillin clavulanate + ciprofloxacin	Ciprofloxacin	Treatment with amoxicillin-clavulanate 1g tib and ciprofloxacine 750mg bid for 5 days

Primary Outcome Measures

Name	Time	Method
Success rate	7 days	The success rate is defined by the proportion of patients receiving the tested regimen: * with resolution of fever ≤72h after the start of antibiotics (total duration of antibiotics expected : 5 days); * AND without any modification of the antibiotic regimen (route, dosage, combination total duration of antibiotics expected : 5 days),; * AND without fever recurrence in 48h following the discontinuation of antibiotics (so end of the measure of the main outcome at day 7).