Effect on Adrenal Function of Budesonide Versus Fluticasone in Chronic Obstructive Pulmonary Disease (COPD)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 4

Summary: 
      National Institute for Clinical Excellence (NICE) guidelines recommend high dose inhaled
      steroids for patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD, a
      common chronic disease related to smoking) who are having two or more exacerbations requiring
      treatment with antibiotics or oral steroids in a 12 month period. The preparations licensed
      for this indication commercially available are Symbicort® and Seretide®. High dose inhaled
      steroids (contained in both) can cause suppression of the adrenal glands. The investigators
      want to assess adrenal suppression caused by the two preparations and compare. The results
      could guide investigators in prescribing these preparations.
    

Detailed description: 
      Background COPD is a very common disease which is chronic and progressive. Current NICE
      guidelines recommend the use of inhaled steroid in relatively high dose in patients with
      moderate to severe disease who are having two or more exacerbations requiring treatment with
      antibiotics or oral steroids in a 12 month period.The aim of this treatment is to reduce the
      exacerbation rates and slow decline in health status. None of the inhaled steroids currently
      available are licensed for use alone in the treatment of COPD. They are prescribed in
      combination with a long acting beta 2 agonist (LABA, a medication which leads to dilatation
      of the airways), which is an effective combination. The combination of a LABA with inhaled
      steroid preparations available includes Symbicort® (containing budesonide and formoterol
      fumarate and Seretide® (containing fluticasone propionate and salmeterol xinafoate).
      Symbicort® has been evaluated in randomized controlled in patients with COPD and has been
      found to be beneficial compared to either component alone. Similar data is available for
      Seretide® as well. There are no large trials directly comparing the two different
      preparations and quite often the choice between the two is made rather empirically. Although
      inhaled steroids have a very good safety profile at low doses, the dose used in both these
      preparations for use in COPD is high and has got potential for adverse effects such as
      adrenal (a gland in the body which secretes steroids) suppression. Studies have shown that
      marked adrenal suppression occurs with high dose inhaled steroids.However the doses used in
      various studies have been different and these studies have been in the asthmatic group of
      patients, the response of whom may be different from those with COPD. The effect of adrenal
      function can be assessed by a simple analysis of an overnight urine sample collection. It is
      difficult to decide which of the treatments to choose on initiation of therapy. We wish to
      compare the adrenal suppression between the two treatments and determine whether there is any
      difference, which could influence decision on treatment in specific patient groups who are
      considered more at risk for adverse effects. Study design This study will be conducted at a
      single centre. The investigators will be responsible for the study. The study is designed as
      an 8 week study in which patients will cross over from one arm of the study group to another.
      Patients with COPD who are on current treatment with either Symbicort® or Seretide® on doses
      as per NICE guidelines will be included. The treatment doses are Symbicort® (budesonide /
      formoterol, 400 micrograms/9 micrograms) one puff bd and Seretide® (fluticasone/salmeterol,
      250 micrograms/25 micrograms) two puffs bd. We plan to include 30 patients either on current
      treatment with Symbicort® or Seretide®. On visit 1 : Patients would either be on treatment
      with high dose Symbicort® OR Seretide® (on treatment for at-least four weeks). The patients
      will be re-trained in the correct use of their current inhaler and re-educated has to how
      often they should be taking the medication. The patient will be guided to take the treatment
      as indicated for 4weeks, at the end of the 4 week treatment they will be asked to collect an
      overnight (12 hrs) urine sample (21:00 hrs-09:00hrs). The patient will return to the clinic
      for visit 2 where they will return the urine sample and quality of life in the previous 4
      weeks will be assessed by means of a modified St Georges Respiratory questionnaire. If the
      patient was on treatment with Symbicort® it will be switched over to Seretide® and
      vice-versa. The patient will be seen 4 weeks later on visit 3.

      A bottle for collecting an overnight ( 12 hours) urine sample will be given to the patient
      for urine collection at the end of the 4 week treatment period. On visit 3: the patient will
      return the overnight urine sample and The quality of life of the patient in the previous 4
      weeks will be assessed using the modified St Georges Respiratory Questionnaire.
    

Intervention name(s): budesonide / formoterol; fluticasone/salmeterol
Intervention type(s): Drug; Drug
Intervention description(s): budesonide / formoterol, 400 micrograms/9 micrograms one IH bd; fluticasone/salmeterol, 250 micrograms/25 micrograms two puffs bd, dose as per NICE guidelines
Other intervention name(s): Symbicort; Seretide
Intervention MeSH terms: Fluticasone; Budesonide; Formoterol Fumarate; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment