Clinical trial NCT02338362: Inhaled Corticosteroids: Effect on Intraocular Pressure in Patients With Controlled Glaucoma
Official title: The Effect of Inhaled Corticosteroids on Intraocular Pressure in Patients With Ocular Hypertension or Controlled Glaucoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ocular Hypertension
Glaucoma, Open-Angle
Keywords: Corticosteroids
Bronchodilator Agents
Intraocular Pressure
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to determine whether a commonly prescribed orally inhaled corticosteroid treatment will induce a clinically meaningful elevation in intraocular pressure, when administered to patients with ocular hypertension (OHT) or open-angle glaucoma (OAG). Based on the response to high-dose corticosteroids, this patient group is more likely than the normal population to demonstrate this adverse effect.

Detailed description: Systemic and topical ophthalmic steroids have long been associated with ocular effects, such as glaucoma or cataracts.\[Alfano JE; Bernstein HN et al. 1962; Bernstein HN et al. 1963; Becker B and Mills DW in Arch Ophthalm 1963; Becker B and Mills DW in JAMA 1963; Armaly MF 1963 (1); Armaly MF 1963 (2); and Buckley RJ\] Periocular steroid injections \[Herschler J; Kalina RE\] and steroids applied to periocular skin \[Aggarwal RK et al.\] have also been reported to increase intraocular pressure (IOP) and raised IOP is the major risk factor for glaucoma.

Ocular hypertension (OHT) is defined as an IOP above 21mmHg in one or both eyes without detectable glaucomatous damage. Primary open-angle glaucoma (POAG) is a chronic and progressive optic neuropathy of unknown etiology characterized by disc cupping, and often associated with visual field defects and elevated IOP. This disease is one of the leading causes of blindness worldwide.\[Kwon YH et al.\] Approximately 18% to 36% of the general population are corticosteroid responders. This response is increased to 46% to 92% in patients with POAG.\[Tripathi RC et al.\] Asthma is the most common chronic respiratory illness in Canada, affecting approximately 10% of the population. For the majority of these patients, long-term inhaled corticosteroids (ICS) are standard of care to prevent acute asthma exacerbations.\[Kim H and Mazza J\] Although the systemic absorption of inhaled and nasal steroids has been established, the clinically relevant ocular side effects are poorly defined. \[Cave A et al.; Allen DB et al.\] A large prospective study in 1995 by Samiy et al reported no statistically significant increase of IOP in 187 patients without glaucoma taking inhaled steroids for various pulmonary conditions.\[Samiy N et al.\] However, six cases of increased IOP associated with combined nasal and inhaled steroid use in non-glaucomatous patients have been reported. \[Dreyer EB; Desnoeck M et al.; Opatowsky I et al.\] A large case-control study in 1997 suggested that current users of high doses of ICS prescribed regularly for 3 or more months were at increased risk of OHT or OAG (OR 1.44; 95% CI 1.01-2.06).\[Garbe E et al.\] In contrast, Gozalez et al. conducted a nested case-control study in 2010 with Quebec data which showed current and continuous use of ICS did not result in increased risk of glaucoma or raised IOP requiring treatment.\[Gonzalez AV et al.\] Similarly, Duh et al. reported no association between inhaled budesonide daily therapy and increased IOP in 1255 asthmatic patients.\[Duh MS et al.\] Further, a prospective population-based cohort study published in 2012 suggested no association between the development of OAG and ICS in the elderly.\[Marcus MW et al.\] In 2013, our group published a randomized double-masked controlled trial that showed no evidence of IOP elevation after 6 weeks use of beclomethasone nasal spray in 19 patients with OHT and POAG.\[Yuen D et al.\] The purpose of the current study protocol would be to extend the study to investigate ICS in the same patient population.

To date, the effect of inhaled corticosteroids in those with pre-existing OHT or POAG remains uncertain. Considering the large number of patients on inhaled steroids, investigating the use of inhaled steroid in glaucoma patients could have significant clinical impact. This study was designed to evaluate the effect of inhaled fluticasone propionate on intraocular pressure (IOP) in patients with OHT or controlled open-angle glaucoma (OAG).

Patient randomization was performed by an independent Research Coordinator in a separate physical space and kept sealed from the principal study investigators, who assessed and recorded outcome measures, until the completion of study data collection. IOP was measured in a masked fashion, using a second observer to record values. Two measurements within 1 mmHg were averaged for each data point. With a sample size of 8 patients per interventional arm, the study is powered at 0.80 to detect an elevation of 3.2 mmHg (≥20%) from mean, assuming a standard deviation of 2.5 mmHg. Baseline data will be compared between groups using the student's t test and Fisher exact test. A 2-sided p value of \<0.05 will be considered statistically significant. The primary outcome measure (mean IOP) will be assessed using a 1-sided Student t test.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 85 years, inclusive
* Mild-moderate open-angle glaucoma/ocular hypertension with cup:disc ratio \<0.85 vertically and humphrey visual field mean deviation \>-12.00 (BOTH EYES must meet this criteria for patient to be included)
* Glaucoma well-controlled, defined by IOP \< 21 mmHg and at target with no visual field/disc progression for at least 6 months (BOTH EYES must meet this criteria for patient to be included)

Exclusion Criteria:

* Any form of steroid medication use within the prior 6 weeks
* Any previous intra-ocular surgery or refractive surgery in the study eye
* no light perception (i.e. blindness) in either eye
* unwilling/unable to give consent
* unwilling to accept randomization
* patient potentially unavailable for follow-up visits

Primary outcomes:
measure: Mean Intraocular Pressure
timeFrame: week 6
Secondary outcomes:
measure: Mean Visual Acuity
timeFrame: week 6
measure: Side Effects
timeFrame: from baseline to week 6
measure: Intraocular Pressure Elevation >20% From Baseline
timeFrame: within 6-week observation period
measure: Adherence
timeFrame: Completion of study, up to 6 weeks
Other outcomes:
Locations:
Study officials:
affiliation: University Health Network, Toronto Western Hospital
name: Graham E Trope, MD,PhD,FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: ALFANO JE. CHANGES IN THE INTRAOCULAR PRESSURE ASSOCIATED WITH SYSTEMIC STEROID THERAPY. Am J Ophthalmol. 1963 Aug;56:245-7. doi: 10.1016/0002-9394(63)91858-0. No abstract available.
citation: BERNSTEIN HN, SCHWARTZ B. Effects of long-term systemic steroids on ocular pressure and tonographic values. Arch Ophthalmol. 1962 Dec;68:742-53. doi: 10.1001/archopht.1962.00960030746009. No abstract available.
citation: BERNSTEIN HN, MILLS DW, BECKER B. Steroid-induced elevation of intraocular pressure. Arch Ophthalmol. 1963 Jul;70:15-8. doi: 10.1001/archopht.1963.00960050017005. No abstract available.
citation: BECKER B, MILLS DW. CORTICOSTEROIDS AND INTRAOCULAR PRESSURE. Arch Ophthalmol. 1963 Oct;70:500-7. doi: 10.1001/archopht.1963.00960050502012. No abstract available.
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