ACACIA: 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.

Sponsor

Poitiers University Hospital (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04698057

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Febrile Neutropenia	Drug: Placebo Drug: Amoxicillin Clavulanate Drug: Ciprofloxacin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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.

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Amoxicillin clavulanate + ciprofloxacin Treatment with amoxicillin-clavulanate 1g tib and ciprofloxacine 750mg bid for 5 days	Drug: Amoxicillin Clavulanate Will be administred to all patients Drug: Ciprofloxacin Will be administred to patients in the standard of care arm
Experimental: Amoxicillin clavulanate + Placebo Treatment with amoxicillin-clavulanate 1g tib for 5 days	Drug: 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 Drug: Amoxicillin Clavulanate Will be administred to all patients

Arm

Intervention/Treatment

Active Comparator: Amoxicillin clavulanate + ciprofloxacin

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

Drug: Amoxicillin Clavulanate

Will be administred to all patients

Drug: Ciprofloxacin

Will be administred to patients in the standard of care arm

Experimental: Amoxicillin clavulanate + Placebo

Treatment with amoxicillin-clavulanate 1g tib for 5 days

Drug: 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

Drug: Amoxicillin Clavulanate

Will be administred to all patients

Outcome Measures

Primary Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 110 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).