Study to Reduce Duration of Antibiotic Therapy in Haematological Patients With Fever and Neutropenia (HOWLONG)

Randomized Open Label Clinical Trial Directed to Optimize the Duration of Empirical Antimicrobial Therapy in Haematologic Patients With Febrile Neutropenia

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

Study Overview

• Status: Completed
• Conditions: Febrile Neutropenia
• Intervention / Treatment: Drug: Empirical antimicrobial treatment discontinuation; Drug: Standard empirical antimicrobial treatment discontinuation

Detailed Description

The optimal duration of the empirical antimicrobial therapy (AT) in hematological patients with febrile neutropenia (FN) is unknown. The Infectious Diseases Society of America (IDSA) recommends maintaining AT at least until the neutropenia is recovered, because literally "years of experience have proven this approach to be safe and effective". This recommendation is likely to cause unnecessarily prolonged treatments, and is against the urgent need of optimizing the antimicrobial therapy proposed by IDSA. The main objective of this study is to establish whether an individualized clinical protocol is better than the standard criteria (recovery of neutropenia as the criterion to suspend the empirical AT in hematological patients with FN).

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clínic
  • Barcelona, Spain, 08907
    • Bellvitge University Hospital
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Seville, Spain, 41013
    • Virgen del Rocio University Hospital
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • Hospital de Jerez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (equal or older than 18 years) of both sexes admitted in the Department of Clinical Hematology who develop a febrile neutropenia. Including fever with unknown source and fever secondary to infection focus of clinical diagnosis without laboratory confirmation.
• Informed consent signed.

Exclusion Criteria:

• Fever with etiologic diagnosis.
• Patients with epilepsy.
• Pregnant or lactating women.
• Patients with HIV infection.
• Patients with severe renal failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; Empirical antimicrobial treatment discontinuation	Drug: Empirical antimicrobial treatment discontinuation; Empirical antimicrobial treatment discontinuation will occur when the patient is: Afebrile, with resolution of signs, symptoms and test abnormalities secondary to complementary source of infection and with normalization of vital signs for ≥ 72 h.; Other Names: Clinical rules for finalization of antimicrobial therapy
Active Comparator: Control Arm; Standard empirical antimicrobial treatment discontinuation	Drug: Standard empirical antimicrobial treatment discontinuation; The empirical antimicrobial treatment discontinuation will occur when the patient is: The neutrophil count is above 500 million per mm3.; Other Names: Laboratory rules for finalization of antimicrobial therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days on which patient is free of antimicrobial treatment	Protocol visits: Screening visit, Randomization visit, at 72h. of apyrexy (visit 1), at clinical recovery (visit 2), at recovery of neutropenia (visit 3), at relapsing fever (visit 4) and at 28 days (final visit).	28 days following the initiation of empiric antibiotic treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crude mortality	Number of died patients	28 days following the initiation of empiric antibiotic treatment.
Number of days of fever	Number of days of fever	28 days following the initiation of empiric antibiotic treatment

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Study Director: José M Cisneros Herreros, PhD, Virgen del Rocío University Hospital/ Biomedicine Institute of Seville (IBIS)

Publications and helpful links

General Publications

• Aguilar-Guisado M, Espigado I, Martin-Pena A, Gudiol C, Royo-Cebrecos C, Falantes J, Vazquez-Lopez L, Montero MI, Rosso-Fernandez C, de la Luz Martino M, Parody R, Gonzalez-Campos J, Garzon-Lopez S, Calderon-Cabrera C, Barba P, Rodriguez N, Rovira M, Montero-Mateos E, Carratala J, Perez-Simon JA, Cisneros JM. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017 Dec;4(12):e573-e583. doi: 10.1016/S2352-3026(17)30211-9. Epub 2017 Nov 15.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: April 17, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimate): April 20, 2012

Study Record Updates

• Last Update Posted (Actual): November 1, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: procalcitonin; febrile neutropenia; antimicrobial treatment
• Additional Relevant MeSH Terms: Wounds and Injuries; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Body Temperature Changes; Heat Stress Disorders; Neutropenia; Hyperthermia; Fever; Febrile Neutropenia; Anti-Bacterial Agents; Anti-Infective Agents
• Other Study ID Numbers: 2011-005152-34