Clinical trial to reduce duration of antibiotic therapy in "in-hospital" patients with haematological diseases that develop fever and low white blood cell count (neutropenia).

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2011-005152-34-ES
• Date of registration: 22/11/2011
• Prospective Registration: Yes
• Primary sponsor: José Miguel Cisneros Herreros
• Public title: Clinical trial to reduce duration of antibiotic therapy in "in-hospital" patients with haematological diseases that develop fever and low white blood cell count (neutropenia).
• Scientific title: Randomized open label clinical trial directed to optimize the duration of empirical antimicrobial therapy in haematologic patients with febrile neutropenia
• Date of first enrolment: 26/03/2012
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005152-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: standard procedure for the withdrawal of treatment: neutrophil levels greater than 500 cells per mm3 Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Fernando Pérez Martínez
• Affiliation: Unidad de Investigación Clínica y Ensayos Clínicos

• Name: Fernando Pérez Martínez
• Affiliation: Unidad de Investigación Clínica y Ensayos Clínicos

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult patients (equal or older than 18 years) of both sexes.
2. Hospital admission in the Department of Clinical Hematology
3. With any of the following diagnoses:
a. leukemia
b. lymphoproliferative syndrome
c. multiple Myeloma
d. myelodysplastic syndrome
e. bone marrow aplasia
f. Patients likely to receive autologous or allogeneic hematopoietic stem cell trasplant.
4. Febrile neutropenia. Including fever with unknown source and fever secondary to infection focus of clinical diagnosis without laboratory confirmation.
5. Informed consent signed.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
1. Fever with etiologic diagnosis. Including fever from infectious etiology, fever caused by non-infectious causes such as transfusions, drugs, graft versus host disease (GVHD) or fever due to underlying disease.
2. Patients in whom, predictably, the duration of treatment will be adjusted following the recommendations established for the specific diagnosis of fever.
3. Patients with known allergies or history of hypersensitivity to acyclovir, valaciclovir, valganciclovir, ganciclovir, amphotericin, aztreonam, ciprofloxacin, piperacillin-tazobactam, amikacin, aminoglycosides, imipenem, itraconazole, cilastatin sodium, meropenem, vancomycin, caspofungin, levofloxacin, voriconazole, posaconazole, any other beta-lactam antibiotic (eg.: penicillins and cephalosporins), any other beta-lactamase inhibitor or any other quinolone.
4. Patients with epilepsy
5. Patients with a history of tendon disorders related to fluoroquinolone administration.
6. Pregnant or lactating women.
7. Patients with HIV infection.
8. Patients with severe renal impairment (defined as creatinine clearance below 30 ml / min)
9. Patients receiving medication substrates of CYP3A4 (ergot alkaloids ergotamine and dihydroergotamine, terfenadine, astemizole, cisapride, pimozide or quinidine, rifampin, carbamazepine, phenobarbital, high doses of ritonavir (400 mg and above twice daily) herb St. John's Wort.
10. Participation, currently or three months before, in other clinical trials in the therapy or intervention that could interfere with the results of this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

In-hospital adult patients diagnosed with acute leukemia, lymphoproliferative syndrome, multiple myeloma, myelodysplastic syndrome, aplastic anemia or who have received autologous or allogeneic transplantation of hematopoietic progenitors, with febrile neutropenia without etiological diagnosis.
MedDRA version: 14.0 Level: PT Classification code 10016288 Term: Febrile neutropenia System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 14.0 Level: LLT Classification code 10066156 Term: Empiric treatment System Organ Class: 10042613 - Surgical and medical procedures

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Intervention(s)

Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: ACICLOVIR
CAS Number: 59277-89-3
Current Sponsor code: NA
Other descriptive name: ACICLOVIR
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: range
Concentration number: 5-10

Pharmaceutical Form: Solution for injection
INN or Proposed INN: AMIKACIN
CAS Number: 37517-28-5
Current Sponsor code: NA
Other descriptive name: AMIKACIN
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 20-

Pharmaceutical Form: Powder for solution for injection or infusion
INN or Proposed INN: AMPHOTERICINE B, LIPOSOME
CAS Number: 8000078-82-2
Current Sponsor code: NA
Other descriptive name: AMPHOTERICINE B, LIPOSOME
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: range
Concentration number: 3-10

Pharmaceutical Form: Powder for solution for injection or infusion
INN or Proposed INN: CASPOFUNGIN ACETATE
CAS Number: 179463-17-3
Current Sponsor code: NA
Other descriptive name: CASPOFUNGIN ACETATE
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 50-70

Pharmaceutical Form: Powder for solution for injection or infusion
INN or Proposed INN: CEFEPIME DIHYDROCHLORIDE MONOHYDRATE
CAS Number: NA
Current Sponsor code: NA
Other descriptive name: CEFEPIME DIHYDROCHLORIDE MONOHYDRATE
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 6-

Pharmaceutical Form: Solution for infusion and oral solution
INN or Proposed INN: CIPROFLOXACIN
CAS Number: 85721-33-1
Current Sponsor code: NA
Other descriptive name: CIPROFLOXACIN
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 800-1500

Pharmaceutical Form: Tablet
INN or Proposed INN: TRIMETHOPRIM SULFATE
CAS Number: 56585-33-2
Current Sponsor code: NA
Other descriptive name: TRIMETHOPRIM SULFATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-
INN or Proposed INN: SULFAMETH

Primary Outcome(s)

Primary end point(s): Number of days on which patient is free of antimicrobial treatment

Main Objective: To establish whether an individualized clinical protocol is better than the recovery from neutropenia (standard criteria) to decide the withdrawal of empirical antimicrobial therapy in haematological patients with febrile neutropenia (FN).

Secondary Objective: 1. To demonstrate that the individualized clinical protocol is as safe as the standard criteria, comparing:
a. The crude mortality within 28 days after the initiation of empiric antibiotic treatment.
b. The number of days of fever within 28 days after the initiation of empiric antibiotic treatment.
2. To analyze the relationship of procalcitonin (PCT) with the appearance of relapsing fever and its potential usefulness as a guide to decide the duration of empiric antibiotic treatment in patients with haematologic NF.

Timepoint(s) of evaluation of this end point: all the protocol visits

Secondary Outcome(s)

Secondary end point(s): - Crude mortality within 28 days after the initiation of empiric antibiotic treatment.
- Number of days of fever within 28 days following the initiation of empiric antibiotic treatment.
- Value of a more favorable of procalcitonin level to predict relapsing fever.

Timepoint(s) of evaluation of this end point: 1. Mortality in the final visit. 2. Fever at visit 1. 3 Procalcitonin value in the Screening visit, randomization, at 72h. of apirexy (visit 1), at clinical recovery, at relapsing fever and at 28 days (final visit)

Secondary ID(s)

HOWLONG

Source(s) of Monetary Support

Fondo de Investigación Sanitaria, convocatoria 2011 expediente PI11/02674