Back to resultsAmoxicillin-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. (ACACIA)
Primary Purpose
Febrile Neutropenia
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Placebo
Amoxicillin Clavulanate
Ciprofloxacin
Sponsored by
About this trial
This is an interventional treatment trial for Febrile Neutropenia
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).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Amoxicillin clavulanate + ciprofloxacin
Amoxicillin clavulanate + Placebo
Arm Description
Treatment with amoxicillin-clavulanate 1g tib and ciprofloxacine 750mg bid for 5 days
Treatment with amoxicillin-clavulanate 1g tib for 5 days
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Full Information
NCT ID
NCT04698057
First Posted
January 4, 2021
Last Updated
March 16, 2022
Sponsor
Poitiers University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04698057
Brief 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.
Acronym
ACACIA
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.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Withdrawn
Why Stopped
No enrolment due to Covid-19
Study Start Date
March 1, 2022 (Anticipated)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Poitiers University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Febrile Neutropenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Amoxicillin clavulanate + ciprofloxacin
Arm Type
Active Comparator
Arm Description
Treatment with amoxicillin-clavulanate 1g tib and ciprofloxacine 750mg bid for 5 days
Arm Title
Amoxicillin clavulanate + Placebo
Arm Type
Experimental
Arm Description
Treatment with amoxicillin-clavulanate 1g tib for 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Intervention Name(s)
Amoxicillin Clavulanate
Intervention Description
Will be administred to all patients
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin
Intervention Description
Will be administred to patients in the standard of care arm
Primary Outcome Measure Information:
Title
Success rate
Description
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).
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
110 Years
Accepts Healthy Volunteers
No
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).
12. IPD Sharing Statement
Learn more about this trial
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.
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