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Inhaled Corticosteroids: Effect on Intraocular Pressure in Patients With Controlled Glaucoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02338362
Recruitment Status : Completed
First Posted : January 14, 2015
Results First Posted : May 3, 2019
Last Update Posted : May 3, 2019
Sponsor:
Information provided by (Responsible Party):
Graham E Trope, University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Ocular Hypertension Glaucoma, Open-Angle Drug: Fluticasone propionate inhaler Drug: Saline placebo inhaler Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: The Effect of Inhaled Corticosteroids on Intraocular Pressure in Patients With Ocular Hypertension or Controlled Glaucoma.
Study Start Date : September 2014
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Glaucoma Steroids

Arm Intervention/treatment
Active Comparator: Fluticasone
10 participants will be asked to use fluticasone propionate 250 µg metered-dose inhaler 1 puff twice-daily for 6 weeks.
Drug: Fluticasone propionate inhaler
fluticasone propionate 250 µg metered-dose inhaler

Placebo Comparator: Saline placebo
10 participants will be asked to use a saline placebo metered-dose inhaler 1 puff twice-daily for 6 weeks.
Drug: Saline placebo inhaler
saline metered dose inhaler




Primary Outcome Measures :
  1. Mean Intraocular Pressure [ Time Frame: week 6 ]
    Masked assessment of intraocular pressure using goldmann application tonometry. Mean of 2 measurements within 1 mmHg will be recorded.


Secondary Outcome Measures :
  1. Mean Visual Acuity [ Time Frame: week 6 ]
    best corrected logMAR visual acuity for each eye. 20/20 vision corresponds with a logMAR score of 0, while negative logMAR scores indicate better than 20/20 vision, values > 0.5 correspond with low vision, and values > 1.3 correspond with blindness.

  2. Side Effects [ Time Frame: from baseline to week 6 ]
    subjective (reported) and objective (slit lamp examination) side-effects attributable to study medications

  3. Intraocular Pressure Elevation >20% From Baseline [ Time Frame: within 6-week observation period ]
    Participants with 2 consecutive intraocular pressure measurements exceeding 20% increase from baseline were discontinued from study.

  4. Adherence [ Time Frame: Completion of study, up to 6 weeks ]
    Adherence was calculated from self-reported study diaries and correlated to a counter that measured number of inhaled puffs built into the placebo metered-dose inhalers



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02338362


Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Graham E Trope, MD,PhD,FRCSC University Health Network, Toronto Western Hospital
Publications:

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Responsible Party: Graham E Trope, Toronto Western Hospital Glaucoma Service Co-Director, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02338362    
Other Study ID Numbers: 13-6069-A
First Posted: January 14, 2015    Key Record Dates
Results First Posted: May 3, 2019
Last Update Posted: May 3, 2019
Last Verified: April 2019
Keywords provided by Graham E Trope, University Health Network, Toronto:
Corticosteroids
Bronchodilator Agents
Intraocular Pressure
Additional relevant MeSH terms:
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Glaucoma
Ocular Hypertension
Glaucoma, Open-Angle
Hypertension
Vascular Diseases
Cardiovascular Diseases
Eye Diseases
Fluticasone
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents