Prednisolone Rhinosinusitis Efficacy Trial (PRET) study

*Rhinosinusitis-like symptoms* (RS) is an important medical entity in general
practice, with an incidence of approximately 25 per 1000 patients per year.
Generally RS is a self-limiting disease lasting one to four weeks. There is an
ongoing discussion on the aetiology of RS. Till recent years, the point of view
was to consider RS as a bacterial infection to be treated with antibiotics,
despite most randomized placebo controlled trials with antibiotics in RS
patients failed to show an overall beneficial effect. Therefore, there is
nowadays a strong tendency among physicians, as well as researchers, that RS
should be regarded more as an inflammatory than an infectious disease entity.
As a consequence, guidelines of the Dutch College of General Practitioners on
treatment of RS recommend symptomatic treatment with analgesics and
decongestive nosedrops (xylomethazoline) during the first two weeks. Despite
pain reduction and decongestive therapy, this period is long and inconvenient
for most patients as RS is often accompanied with insomnia, loss of appetite,
feeling unwell and absence of work/school. This, together with patient
expectation in favour for antibiotics, is probably the main reason for high
prescription rates of antibiotics in patients during episodes of RS in general
practice. Antibiotics are namely prescribed in minimally 70% of these episodes,
leading to considerable costs and unwanted side-effects, besides, most notably
inducing bacterial resistance. In line with the pathophysiological
consideration mentioned above - to regard RS rather as an inflammatory disease
- it has been hypothesized to treat patients with ongoing RS with intranasal
and/or systemic corticosteroids to reduce inflammation and enhance clearance of
the sinuses. Till date no clear scientific evidence is available to support (or
reject) this hypothesis; the evidence on use of INCS in RS is conflicting,
while there is limited evidence that short course of systemic steroids (as
additive therapy to antibiotics) is beneficial in patients with RS. Whether a
short course of oral steroids, as a monotherapy, is cost-effective in the large
population of patients with RS is unknown.

To assess the effects of a 7-day course of 30 mg prednisolone daily in addition
to usual care (symptomatic) treatment in adults with RS.

Double-blind placebo controlled randomized clinical trial.

A 7 day course of 30 mg prednisolone per os once daily in addition to
xylomethazoline nasal spray q8h for 7 days (usual care).

A short course of systemic prednisolone (30 mg prednisolone q24h during 7 days)
has been successfully prescribed in inflammatory disease entities like
exacerbations of asthma and COPD, diminishing signs and symptoms of the lower
airways, and as a consequence accelerate recovery significantly. This treatment
may shorten the duration of symptoms in RS as well. As a result, this will
diminish school/work absenteeism, use of analgesics and antibiotics (as well as
its side-effects) and lead to a decrease in sleeping disorders. In addition,
the incidence of secondary bacterial infections (now about 5%) might be
reduced. Furthermore, the potential benefit of prednisolone treatment could
result in a massive reduction of medical costs.
Importantly, steroid use may confer side-effects, although mainly among
patients receiving these drugs for prolonged periods. A literature search was
performed to identify potential side-effects of a short course of prednisolone
therapy. None of these studies did show any information to be considered
relevant and did not lead to discontinuation of study interventions. However,
side-effects could also occur during a one week treatment period. As a
consequence, these will be closely monitored. All contacts of included patients
will be monitored for a follow up of eight weeks. The side-effects of
prednisolone will be determined and balanced against the potential benefits.

The burden associated with participation includes two GP visits (day 1 and day
14). The GP will perform a standardised history taking and physical exam during
these visitis. Besides, the subjects are asked to complete a diary during 14
days (general questions, daily symptomscore, questionnaire at day 14) and to
complete a telephone questionnaire at the end of the study period of eight
weeks.