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.

NCT ID: NCT04698057

Last Updated: 2022-03-31

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2025-06-01

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.

Conditions

Febrile Neutropenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amoxicillin clavulanate + ciprofloxacin

Treatment with amoxicillin-clavulanate 1g tib and ciprofloxacine 750mg bid for 5 days

Group Type: ACTIVE_COMPARATOR

Amoxicillin Clavulanate

Intervention Type: DRUG

Will be administred to all patients

Ciprofloxacin

Intervention Type: DRUG

Will be administred to patients in the standard of care arm

Amoxicillin clavulanate + Placebo

Treatment with amoxicillin-clavulanate 1g tib for 5 days

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

The aim of the study is to validate the desescalation of the treatment to stop ciprofloxacin prescription that may not impact the outcome of the patients but add toxicity and antibiotics selection. Placebo will be administred in the experimental arm

Amoxicillin Clavulanate

Intervention Type: DRUG

Will be administred to all patients

Interventions

Placebo

The aim of the study is to validate the desescalation of the treatment to stop ciprofloxacin prescription that may not impact the outcome of the patients but add toxicity and antibiotics selection. Placebo will be administred in the experimental arm

Intervention Type: DRUG

Amoxicillin Clavulanate

Will be administred to all patients

Intervention Type: DRUG

Ciprofloxacin

Will be administred to patients in the standard of care arm

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 110 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Poitiers University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

ACACIA

Identifier Type: -

Identifier Source: org_study_id