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.

NCT04698057 | Withdrawn Phase 3 DMC

• 1 other identifier: ACACIA
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Success rate

  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).

  7 days

Study Arms (2)

Amoxicillin clavulanate + ciprofloxacin

ACTIVE COMPARATOR

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

Drug: Amoxicillin Clavulanate; Drug: Ciprofloxacin

Amoxicillin clavulanate + Placebo

EXPERIMENTAL

Treatment with amoxicillin-clavulanate 1g tib for 5 days

Drug: Placebo; Drug: Amoxicillin Clavulanate

Interventions

Placebo 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 + Placebo

Amoxicillin Clavulanate DRUG

Will be administred to all patients

Amoxicillin clavulanate + Placebo; Amoxicillin clavulanate + ciprofloxacin

Ciprofloxacin DRUG

Will be administred to patients in the standard of care arm

Amoxicillin clavulanate + ciprofloxacin

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Poitiers University Hospital: lead

MeSH Terms

Conditions

Febrile Neutropenia

Interventions

Amoxicillin-Potassium Clavulanate Combination; Ciprofloxacin

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 6, 2021
• Study Start: March 1, 2022
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: March 31, 2022

Record last verified: 2022-03