Primary Open-Angle Glaucoma, Mild StageNCT03534882
Effects of Prostaglandin Analogue Washout Following Long-term Therapy in Adults With Primary Open Angle Glaucoma
A study testing Discontinuation of topical prostaglandin analogue therapy in people with Primary Open-Angle Glaucoma, Mild Stage and Glaucoma, Suspect, run by Cindy Hutnik at 1 site in Canada.
Trial summary
A target for glaucoma treatment is the intra-ocular pressure (IOP) which is lowered with medications, laser, or surgical intervention. The efficacy of different medication classes is well understood as their IOP lowering effects have been well documented. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Open-Angle Glaucoma, Mild Stage, Glaucoma, Suspect, Ocular Hypertension
- What is being tested?
- Discontinuation of topical prostaglandin analogue therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 1 siteCanada
- Study dates
- 27 May 2014to 22 Jun 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of glaucoma or or ocular hypertension
- Prostaglandin analogue responder >20% intraocular pressure (IOP) reduction from baseline
- Age >18 years
- Baseline IOP (pre-treatment) ≥21 mmHg
- Prostaglandin analogue treatment duration > 6 months
Who cannot join
- Diagnosis of acute angle closure glaucoma
- Treatment with > 1 glaucoma medication
- Topical steroid > 3 consecutive weeks
- Intraocular surgery in last 6 months prior to enrollment
- Glaucoma laser intervention in last 12 months prior to enrollment
- Best Corrected Visual Acuity (BCVA) < 70 letters (EDTRS or Snellen equivalent)
- Visual field mean deviation <-3
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective, Randomized, Single-blind Controlled Trial of Topical Prostaglandin Analogue Washout Following Chronic Monotherapy in Adults With Suspected or Proper Primary Open Angle Glaucoma
A target for glaucoma treatment is the intra-ocular pressure (IOP) which is lowered with medications, laser, or surgical intervention. The efficacy of different medication classes is well understood as their IOP lowering effects have been well documented. However, beyond the basic biochemical and pharmacokinetic actions, long-term effects of these drugs on IOP have not been adequately studied. Specifically, does long-term use of anti-glaucoma medications have lasting effects on IOP even with subsequent discontinuation of the medication? In Ontario, prostaglandin analogues are the most frequently prescribed first line anti-glaucoma medication. In our study, we examine the lingering IOP-reducing effects of the prostaglandin analogue anti-glaucoma drug class. Our overall objective is to determine if patients previously treated with prostaglandin analogues remain within acceptable treatment ranges 6 weeks after medication discontinuation, and if this IOP differs from pre-treatment baseline values. Half of participants will discontinue their prostaglandin analogue (PGA) treatment for 6 weeks, while the other half will continue their PGA therapy as prescribed by their ophthalmologist. Both groups will be followed closely throughout the 6 weeks to monitor changes in IOP. This can help us understand the lasting effects of medication use and can help better guide clinical care in optimizing glaucoma management, and help direct study designs of future research that involve any therapy secondary to prostaglandin analogue treatment.
Read the detailed description
Quality assurance plan: Paper copies of all registry data is securely stored at the site of data collection. Registry data is first de-identified and then stored in an encrypted Master data excel sheet that only research staff have access to.
Data Checks and Source Data Verification: Data is monitored closely and re-assessed frequently by multiple members of the research team to ensure the accuracy of the Master data excel sheet. Registry data will be compared to paper registry copies and patient medical records to ensure accuracy and completeness.
Standard Operating Procedures:
All patients currently being seen by Dr. Hutnik (~6000) will have their charts reviewed. Personal information will be recorded to allow research staff to contact eligible participants. Clinical information recorded includes: diagnosis, intraocular pressure (IOP) at baseline, IOP at subsequent follow up visits with medication use, medication history, surgical and laser intervention history, visual acuity at baseline and follow-up visits, and visual field mean deviation. Patients fulfilling the inclusion and having none of the exclusion criteria are contacted via telephone by the research staff to invite them to participate in the trial. If they are interested, participants are met with in-person and provided with an information package including a form of consent. Research staff provide detailed description of this study's protocol, risks, and benefits for the patient prior to obtaining informed consent. Patients are also provided with the research teams' contact information should they have any questions or concerns. As part of the information package, participants receive notice that should they experience worrisome signs and symptoms, they should contact their ophthalmologist's office immediately. Following enrolment, participants are given an enveloped that randomizes them two either the control group (continues their eye drop medications) or experimental group (temporarily discontinues eye drop medications). In order to eliminate measurement bias, this allocation is concealed to research staff until completion of the trial. Participants' IOP is measured by Goldmann applanation tonometry at day of allocation (Day 0) and subsequently 7, 21, and 42 days after. In addition, should their IOP increase back to baseline levels prior to their final day of pressure measurement, participants are asked to restart their eye drops and are closely followed to ensure their IOPs return back to their pre-study values. Paper copies of participant signed consent and information form are stored in the research database. Once the assessment is complete, all participants will be debriefed on the nature of the study and potential findings. At the end of trial, participants will resume standard therapy according to Canadian Ophthalmology Society (COS) 2009 Glaucoma Guidelines.
Power analysis using a General Linear Multivariate Model for Power and Sample Size (GLIMMPSE) found that a total patient N value of 87 (154 eyes) was sufficient power for our study
Missing Data: All missing data is documented in the Master data record and will be reported. Participants with missing baseline (pre-treatment) IOP values are excluded from the study. Within-study missing IOP values are accounted for in statistical analysis.
Statistical analysis: Statistical analysis is performed on R. Data is analyzed using a linear mixed effects model fit by restricted maximum likelihood (REML) t-tests with Satterthwaite approximations to compare mean intraocular pressure between control and washout groups at day 0, 7, 21, and 42.
- Being tested
- Discontinuation of topical prostaglandin analogue therapy
- Keywords
- anti-glaucoma medications, glaucoma, prostaglandin analogues, medication washout
- Medical subject headings
- Glaucoma, Open-Angle, Ocular Hypertension, Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Discontinuation of topical prostaglandin analogue therapyOther
Also called Medication washout
Participants are asked to discontinue their prostaglandin analogue eye drops for the designated time period (42 days)
| Study group | Role | What they receive |
|---|---|---|
| Washout | Experimental | Discontinuation of topical prostaglandin analogue therapy: Participants are asked to discontinue (washout) their prostaglandin analogue for 42 days. As the experimental group, the purpose of this arm is to determine the lingering IOP-reducing effects following discontinuation of chronic prostaglandin analogue therapy, and to determine if IOP rises back to baseline (pre-treatment values). Receives: Other: Discontinuation of topical prostaglandin analogue therapy |
| Control | No intervention | Patients are asked to remain on their prostaglandin analogues and continue treatment as prescribed by their ophthalmologist. The purpose of this arm is to minimize bias in intraocular pressure readings. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Day 42 Intraocular Pressure (mmHg)
Measured by Goldmann Applanation Tonometer
Measured: 42 days after starting trial
Secondary outcomes (2)
Day 7 Intraocular Pressure (mmHg)
Measured by Goldmann Applanation Tonometer
Measured: 7 days after starting trial
Day 21 Intraocular Pressure (mmHg)
Measured by Goldmann Applanation Tonometer
Measured: 21 days after starting trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2018
- Study start27 May 2014
- Primary completion22 Jun 2017
- Study completion22 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Primary Open-Angle Glaucoma, Mild StageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This randomized-controlled trial studies patients with primary open angle glaucoma or ocular hypertension currently treated with topical IOP-lowering prostaglandin analogue (PGA) medications. Patients meeting inclusion criteria and having none of the exclusion criteria are contacted. If interested, patients meet research staff to discuss the study protocol and informed consent is obtained. Participants are randomized to one of two groups (A or B). Allocation to group is concealed to physicians. Participants have their IOP measured at Day 0. Group A patients are asked to discontinue their PGA for 42 days. Group B patients continue their medications as prescribed by their physician. Patients are closely followed, where IOP is measured on day 7, 21, and 42 in all participants. Once the assessment is complete, participants are debriefed on the nature of the study and potential findings. At the end of trial, participants resume standard therapy according to CJO 2009 Glaucoma Guidelines.
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cindy Hutnik
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Cindy Hutnik, Western University, Canada
- Investigators
- Cindy ML Hutnik, MD, PhD, Principal investigator, Western University, Department of Ophthalmology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03534882
- Sponsor's protocol ID
- 4834
- Status last verified
- Apr 2019
- First submitted
- 11 May 2018
- Last updated
- 11 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Gordon MO. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002 Jun;120(6):701-13; discussion 829-30. doi: 10.1001/archopht.120.6.701.
PubMed 12049574Tataru CP, Purcarea VL. Antiglaucoma pharmacotherapy. J Med Life. 2012 Sep 15;5(3):247-51. Epub 2012 Sep 25.
PubMed 23049625Lee R, Hutnik CM. Projected cost comparison of selective laser trabeculoplasty versus glaucoma medication in the Ontario Health Insurance Plan. Can J Ophthalmol. 2006 Aug;41(4):449-56. doi: 10.1016/S0008-4182(06)80006-2.
PubMed 16883360Kreidler SM, Muller KE, Grunwald GK, Ringham BM, Coker-Dukowitz ZT, Sakhadeo UR, Baron AE, Glueck DH. GLIMMPSE: Online Power Computation for Linear Models with and without a Baseline Covariate. J Stat Softw. 2013 Sep;54(10):i10. doi: 10.18637/jss.v054.i10.
PubMed 24403868Lim CW, Diaconita V, Liu E, Ault N, Lizotte D, Nguyen M, Hutnik CML. Effect of 6-week washout period on intraocular pressure following chronic prostaglandin analogue treatment: a randomized controlled trial. Can J Ophthalmol. 2020 Apr;55(2):143-151. doi: 10.1016/j.jcjo.2019.08.004. Epub 2019 Nov 8.
PubMed 31712013
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Single-blind Controlled Trial of Topical Prostaglandin Analogue Washout Following Chronic Monotherapy in Adults With Suspected or Proper Primary Open Angle Glaucoma
- ClinicalTrials.gov ID
- NCT03534882
- Acronym / sponsor ID
- 4834
- Keywords
- anti-glaucoma medications, glaucoma, prostaglandin analogues, medication washout
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Cindy HutnikUniversity, hospital or other
- Study start
- 27 May 2014 (actual)
- Primary completion
- 22 Jun 2017 (actual)
- Study completion
- 22 Jun 2017 (actual)
- First posted
- 23 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A target for glaucoma treatment is the intra-ocular pressure (IOP) which is lowered with medications, laser, or surgical intervention. The efficacy of different medication classes is well understood as their IOP lowering effects have been well documented. However, beyond the basic biochemical and pharmacokinetic actions, long-term effects of these drugs on IOP have not been adequately studied. Specifically, does long-term use of anti-glaucoma medications have lasting effects on IOP even with subsequent discontinuation of the medication? In Ontario, prostaglandin analogues are the most frequently prescribed first line anti-glaucoma medication. In our study, we examine the lingering IOP-reducing effects of the prostaglandin analogue anti-glaucoma drug class. Our overall objective is to determine if patients previously treated with prostaglandin analogues remain within acceptable treatment ranges 6 weeks after medication discontinuation, and if this IOP differs from pre-treatment baseline values. Half of participants will discontinue their prostaglandin analogue (PGA) treatment for 6 weeks, while the other half will continue their PGA therapy as prescribed by their ophthalmologist. Both groups will be followed closely throughout the 6 weeks to monitor changes in IOP. This can help us understand the lasting effects of medication use and can help better guide clinical care in optimizing glaucoma management, and help direct study designs of future research that involve any therapy secondary to prostaglandin analogue treatment.
Detailed description
Quality assurance plan: Paper copies of all registry data is securely stored at the site of data collection. Registry data is first de-identified and then stored in an encrypted Master data excel sheet that only research staff have access to.
Data Checks and Source Data Verification: Data is monitored closely and re-assessed frequently by multiple members of the research team to ensure the accuracy of the Master data excel sheet. Registry data will be compared to paper registry copies and patient medical records to ensure accuracy and completeness.
Standard Operating Procedures:
All patients currently being seen by Dr. Hutnik (~6000) will have their charts reviewed. Personal information will be recorded to allow research staff to contact eligible participants. Clinical information recorded includes: diagnosis, intraocular pressure (IOP) at baseline, IOP at subsequent follow up visits with medication use, medication history, surgical and laser intervention history, visual acuity at baseline and follow-up visits, and visual field mean deviation. Patients fulfilling the inclusion and having none of the exclusion criteria are contacted via telephone by the research staff to invite them to participate in the trial. If they are interested, participants are met with in-person and provided with an information package including a form of consent. Research staff provide detailed description of this study's protocol, risks, and benefits for the patient prior to obtaining informed consent. Patients are also provided with the research teams' contact information should they have any questions or concerns. As part of the information package, participants receive notice that should they experience worrisome signs and symptoms, they should contact their ophthalmologist's office immediately. Following enrolment, participants are given an enveloped that randomizes them two either the control group (continues their eye drop medications) or experimental group (temporarily discontinues eye drop medications). In order to eliminate measurement bias, this allocation is concealed to research staff until completion of the trial. Participants' IOP is measured by Goldmann applanation tonometry at day of allocation (Day 0) and subsequently 7, 21, and 42 days after. In addition, should their IOP increase back to baseline levels prior to their final day of pressure measurement, participants are asked to restart their eye drops and are closely followed to ensure their IOPs return back to their pre-study values. Paper copies of participant signed consent and information form are stored in the research database. Once the assessment is complete, all participants will be debriefed on the nature of the study and potential findings. At the end of trial, participants will resume standard therapy according to Canadian Ophthalmology Society (COS) 2009 Glaucoma Guidelines.
Power analysis using a General Linear Multivariate Model for Power and Sample Size (GLIMMPSE) found that a total patient N value of 87 (154 eyes) was sufficient power for our study
Missing Data: All missing data is documented in the Master data record and will be reported. Participants with missing baseline (pre-treatment) IOP values are excluded from the study. Within-study missing IOP values are accounted for in statistical analysis.
Statistical analysis: Statistical analysis is performed on R. Data is analyzed using a linear mixed effects model fit by restricted maximum likelihood (REML) t-tests with Satterthwaite approximations to compare mean intraocular pressure between control and washout groups at day 0, 7, 21, and 42.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This randomized-controlled trial studies patients with primary open angle glaucoma or ocular hypertension currently treated with topical IOP-lowering prostaglandin analogue (PGA) medications. Patients meeting inclusion criteria and having none of the exclusion criteria are contacted. If interested, patients meet research staff to discuss the study protocol and informed consent is obtained. Participants are randomized to one of two groups (A or B). Allocation to group is concealed to physicians. Participants have their IOP measured at Day 0. Group A patients are asked to discontinue their PGA for 42 days. Group B patients continue their medications as prescribed by their physician. Patients are closely followed, where IOP is measured on day 7, 21, and 42 in all participants. Once the assessment is complete, participants are debriefed on the nature of the study and potential findings. At the end of trial, participants resume standard therapy according to CJO 2009 Glaucoma Guidelines.
| Arm | Type | Receives |
|---|---|---|
| Washout | Experimental | Other: Discontinuation of topical prostaglandin analogue therapyDiscontinuation of topical prostaglandin analogue therapy: Participants are asked to discontinue (washout) their prostaglandin analogue for 42 days. As the experimental group, the purpose of this arm is to determine the lingering IOP-reducing effects following discontinuation of chronic prostaglandin analogue therapy, and to determine if IOP rises back to baseline (pre-treatment values). |
| Control | No intervention | –Patients are asked to remain on their prostaglandin analogues and continue treatment as prescribed by their ophthalmologist. The purpose of this arm is to minimize bias in intraocular pressure readings. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of glaucoma or or ocular hypertension
- Prostaglandin analogue responder >20% intraocular pressure (IOP) reduction from baseline
- Age >18 years
- Baseline IOP (pre-treatment) ≥21 mmHg
- Prostaglandin analogue treatment duration > 6 months
Key exclusion criteria (7 listed)
- Diagnosis of acute angle closure glaucoma
- Treatment with > 1 glaucoma medication
- Topical steroid > 3 consecutive weeks
- Intraocular surgery in last 6 months prior to enrollment
- Glaucoma laser intervention in last 12 months prior to enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Discontinuation of topical prostaglandin analogue therapyAlso: Medication washoutParticipants are asked to discontinue their prostaglandin analogue eye drops for the designated time period (42 days) | Other | Washout |
Primary outcome
Day 42 Intraocular Pressure (mmHg)
Time frame: 42 days after starting trial
Measured by Goldmann Applanation Tonometer
2 secondary outcomes
Day 7 Intraocular Pressure (mmHg)
Time frame: 7 days after starting trial
Day 21 Intraocular Pressure (mmHg)
Time frame: 21 days after starting trial
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2019.
- Background: PubMed 12049574Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Gordon MO. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002 Jun;120(6):701-13; discussion 829-30. doi: 10.1001/archopht.120.6.701.
- Background: PubMed 23049625Tataru CP, Purcarea VL. Antiglaucoma pharmacotherapy. J Med Life. 2012 Sep 15;5(3):247-51. Epub 2012 Sep 25.
- Background: PubMed 16883360Lee R, Hutnik CM. Projected cost comparison of selective laser trabeculoplasty versus glaucoma medication in the Ontario Health Insurance Plan. Can J Ophthalmol. 2006 Aug;41(4):449-56. doi: 10.1016/S0008-4182(06)80006-2.
- Background: PubMed 24403868Kreidler SM, Muller KE, Grunwald GK, Ringham BM, Coker-Dukowitz ZT, Sakhadeo UR, Baron AE, Glueck DH. GLIMMPSE: Online Power Computation for Linear Models with and without a Baseline Covariate. J Stat Softw. 2013 Sep;54(10):i10. doi: 10.18637/jss.v054.i10.
- Derived from this study: PubMed 31712013Lim CW, Diaconita V, Liu E, Ault N, Lizotte D, Nguyen M, Hutnik CML. Effect of 6-week washout period on intraocular pressure following chronic prostaglandin analogue treatment: a randomized controlled trial. Can J Ophthalmol. 2020 Apr;55(2):143-151. doi: 10.1016/j.jcjo.2019.08.004. Epub 2019 Nov 8.
- Individual participant dataSharing planned: Undecided
Related trials for Primary Open-Angle Glaucoma, Mild Stage
Not yet recruitingPhase 2
Nicotinamide for Retinal Protection in Primary Open-Angle Glaucoma (NADIR Trial)
Glaucoma, Open-angle, Primary Open Angle Glaucoma (POAG)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cindy ML Hutnik, MD, PhD principal investigator
Western University, Department of Ophthalmology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Discontinuation of topical prostaglandin analogue therapy in people with Primary Open-Angle Glaucoma, Mild Stage and Glaucoma, Suspect, run by Cindy Hutnik at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Day 42 Intraocular Pressure (mmHg) (time frame: 42 days after starting trial). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03534882, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2019.