Procalcitonin Protocol to Shorten the Antibiotic Therapy in Febrile Neutropenia
Condition: Febrile Neutropenia
MeSH terms: Neutropenia; Febrile Neutropenia; Hyperthermia; Fever
Study type: Interventional

Summary: 
      In this study the investigators aim to test if a procalcitonin (PCT) - guided strategy allows
      to reduce the antibiotic use in patients with febrile neutropenia hospitalized in a Brazilian
      tertiary university hospital, causing no harm.
    

Detailed description: 
      Methods

        -  Patients and setting: Prospective controlled randomized interventional study of
           antibiotic therapy in adult with febrile neutropenia.

      The study will be conducted in the University Hospital of the Federal University of Minas
      Gerais, Brazil. This is a 600-bed tertiary hospital, with approximately 1.6 thousands
      hospitalizations/month. Roughly 120 episodes of febrile neutropenia were recorded in the
      first semester of 2007, occurring in 100 patients with hematological leucosis or post-BMT.
      This number rises if one considers other groups of neutropenic patients, such as those with
      neutropenia due chemotherapy for solid tumors, patients with BM aplasia, myelo dysplasia,
      among others,

        -  Interventions:

      As long as the core objective of the study is to test if a PCT-guided protocol allows to
      guide the antibiotic withdrawn in neutropenic patients, only patients with febrile
      neutropenia under antibiotic therapy will be included in the study. They will be submitted to
      the following exams:

        -  Bood samples will be drawn at baseline to blood culture, CRP, blood cells count, ions,
           liver profile and renal function tests. These exams will be repeated according to the
           local protocol followed by the Service of Hematology (see appendix).

        -  A plasma galactomannan test will be performed at baseline in all patients considered for
           inclusion in the study, and repeated at any moment if there is suspicion of Aspergillus
           infection during the follow up.

        -  A chest radiography will also be performed in all participants at baseline, and
           according to clinical indication afterwards.

        -  All patients with abnormal chest radiography at baseline will be submitted to a
           contrasted chest CT (or without contrast if creatinine clearance < 50 ml/min).

        -  Additional complementary exams will be performed as clinically needed.

        -  Circulating PCT measurements will be performed at baseline, and then on day 3 (if
           initial PCT < 0.5) or on day 5 (if initial PCT >0.5).

      Eligible patients will be reassessed for on day 3 (if initial PCT < 0.5) or on day 5 (if
      initial PCT >0.5), and randomized at 1:1 basis to one of the two groups since any exclusion
      criteria (see below) is present at that time:

      Group 1 - PCT group: the interventions on antibiotic therapy will be based on circulating PCT
      levels.

      Group 2 - Control group: antibiotic therapy will be guided by appropriate guidelines, and
      will be left at the discretion of caregivers.

      Patients randomized to the study will undergo daily measurements of plasma PCT levels, and
      kept under antibiotic therapy until a relative reduction of 90% in baseline PCT levels, or a
      value lower than 0.5 ng/ml is reached, and then maintained for additional 48h (two measure).
      Therefore, plasma PCT levels will be measured every 5 days up to the 28th day of follow-up or
      until death or transference, if either occurs first. Patients included in the interventional
      group will be observed for at least 48 hours following antibiotic discontinuation before
      being discharged from the hospital. Extra PCT tests will be performed according to the
      clinical course.

      Apart from the antibiotic therapy, all participants will be managed according to the
      appropriate guidelines. Patients with febrile neutropenia hospitalized in the University
      Hospital of the Federal University of Minas Gerais are routinely cared by an experienced
      hematology specialist together with an infectious diseases consultant. This standard care
      will be offered to all patients included in the study. The final decision regarding
      antibiotic therapy will be always let to the discretion of these specialists.
    

Intervention name(s): procalcitonin; antibiotic therapy
Intervention type(s): Other; Drug
Intervention description(s): plasma PCT measurement; antibiotic therapy use
Intervention MeSH terms: Anti-Bacterial Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: procalcitonin; neutropenia; febrile neutropenia; antibiotic therapy; neutropenic patients