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Trial registered on ANZCTR


Registration number
ACTRN12618001025224
Ethics application status
Approved
Date submitted
14/06/2018
Date registered
19/06/2018
Date last updated
19/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Self-measurement of eye pressure to determine daily fluctuations in patients using glaucoma eye drops
Scientific title
Diurnal Intraocular Pressure Self-monitoring (DIPS) in glaucoma patients on topical medication
Secondary ID [1] 295143 0
NIL
Universal Trial Number (UTN)
U1111-1215-4613
Trial acronym
DIPS
Linked study record
Parent study establishing measurement protocol: ACTRN12615001274561

Health condition
Health condition(s) or problem(s) studied:
Glaucoma 308243 0
Intraocular pressure variability 308244 0
Condition category
Condition code
Eye 307269 307269 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study investigates the effect of two topical medications, both commonly used, for treatment of glaucoma. The therapeutic effect of the medications is to reduce intraocular pressure (IOP) however less understood is how they impact on IOP variation throughout the day. This study is designed to allow comparison of IOP measurements in patients treated with either topical prostaglandin analogue eye drops or beta blocker eye drops. Two groups of patients will be enrolled.

For group 1, current treatment will serve as intervention treatment 1, alternative treatment as intervention treatment 2. Group 2 the two medications tested will be randomised into a intervention treatment 1 (weeks 2-3 of the below outlined protocol) and intervention treatment 2 (weeks 8-9 of the below outlined protocol). In all cases, medication will be adapted to patient needs based on widely accepted clinical protocols (titrated to effect based on 30% reduction in baseline IOP). Clinical effect and adherence will be assessed for safety reasons based on daily review of IOP measurements uploaded by the patient as outlined below.

Medications administered as intervention treatments during this study are:
Latanoprost (prostaglandin analogue): eye drop (solution) for reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.
Timolol 0.25% (beta-blocker): eye drop (solution) for the reduction of elevated intraocular pressure. In clinical trials it has been shown to reduce intraocular pressure in: Patients with ocular hypertension and chronic open-angle glaucoma including aphakic patients.

The measurement of IOP will be obtained with the Icare HOME instrument. Patients will be trained in the use of the ICARE HOME device, a procedure that takes less than five minutes per measurement. After turning the instrument on, the patient will need to load a single-use probe into the tonometer without touching it and briefly (1 second) press the measure button. Subsequently, the probe tip needs to be aligned with the centre of the cornea, preferentially in front of a mirror, by placing the forehead and cheek support in the respective positions as indicated by the eye care professional during training. If placed correctly, the probe base light will appear green. Pressing the measure button will allow the probe to collect a total of 6 measurements within a matter of seconds. Measurements should then be repeated in the other eye. Once finished, the patient should turn off the instrument by pushing the power button until three short beeps are heard and discard the used probe.
• Training will take place in the clinic where the patient usually is seen for their eye health care. The training sessions will be arranged by the research team either via phone call or face-to-face following attendance at their usual eye care appointment.
• Participants will undergo a 30-45-minute training session on how to use the instrument. Participants will have to demonstrate appropriate use of the instrument and pass an accreditation process (as outlined by the manufacturer).
• For eyes that are successfully accredited, participants will be asked to measure IOP at four time points during the day in their habitual environment i.e. immediately upon awakening, before lunch, before dinner, and before going to bed.
• Participants will also be trained in uploading their measurements to a cloud-based database (Icare Clinic) by connecting the instrument to an enabled device (e.g. phone with the application, Icare Export)

Two patient groups will be recruited; each will have their respective timelines due to different baseline medication use.
1) Group 1: Patients who have been diagnosed with glaucoma or ocular hypertension who are already taking a topical medication to reduce intraocular pressure (prostaglandin analogue or beta-blocker)
2) Group 2: Patients with newly with diagnosed glaucoma or ocular hypertension who have been prescribed, but have not started using a topical medication (prostaglandin analogue or beta-blocker)

Group 1: For patients already on topical anti-glaucoma medications
• Week 1: Intervention treatment 1 (existing treatment serving as the comparator)
• Week 2-5: Washout (no treatment)
• Review Appointment: clinical assessment (including goldmann applanation IOP)
• Week 6-7: Intervention treatment 2**
• Final Appointment: clinical assessment and resumption of existing treatment
**Alternative treatment represents a switch from their current medication to the other investigated eye drop. For example, if the patient’s existing medication was a prostaglandin analogue, the alternative treatment would be a beta-blocker & vice versa.

Group 2: For patients who have not yet started topical anti-glaucoma medications.
• Week 1: Baseline (without treatment)
• Weeks 2-3: Intervention treatment 1(prostaglandin analogue or beta-blocker- randomly assigned***)
• Review Appointment: clinical assessment (including goldmann applanation IOP)
• Weeks 4 to 7***: Washout (no treatment): IOP is monitored remotely by the investigators. When IOP returns to baseline levels then the next step is initiated.
• Telephone Call: An investigator will telephone the participant to advise commencement of intervention treatment
• Weeks 8-9****: Intervention treatment 2 (alternative treatment to what was provided in Weeks 2-3)
• Final Appointment: At study conclusion, patients will start treatment that was prescribed prior to baseline.
*** Treatment protocol will be assigned using random number generator once for each participant. All even numbers will default to prostaglandin analogue in the first treatment round, uneven numbers to beta-blocker.
****The actual timing of these washout and treatment periods will be dependent on the time taken for IOP measurements to return to baseline.
Intervention code [1] 301547 0
Treatment: Drugs
Intervention code [2] 301548 0
Treatment: Devices
Comparator / control treatment
Each patient will undergo the complete clinical protocol and serve as their own control (baseline/washout periods)

For group 1: control treatment will be based on IOP measurements of the baseline obtained during the washout period (week 5).

For group 2: control treatment will be based on IOP measurements during the baseline (week 1) and washout (week 7) period.
Control group
Active

Outcomes
Primary outcome [1] 306310 0
Mean intra-ocular pressure (IOP) measured with the ICARE HOME device during intervention periods compared to control period
Timepoint [1] 306310 0
For group 1: Week 6 of the study protocol and after final appointment
For group 2: Weeks 4 and 8 of the study protocol and after final appointment
Primary outcome [2] 306315 0
Variance of IOP measured with the ICARE HOME device during intervention periods compared to control period
Timepoint [2] 306315 0
For group 1: Week 6 of the study protocol and after final appointment
For group 2: Weeks 4 and 8 of the study protocol and after final appointment
Secondary outcome [1] 348161 0
Difference in mean IOP measured with the ICARE HOME device between intervention periods using a prostglandin analogue and a beta-blocker
Timepoint [1] 348161 0
After final appointment

Eligibility
Key inclusion criteria
Group 1: Patients, diagnosed with glaucoma or ocular hypertension who are taking topical medications to reduce intraocular pressure (prostaglandin analogue or beta-blocker)

Group 2: Patients, newly with diagnosed glaucoma or ocular hypertension who have been prescribed (but not yet started taking) a topical medication (prostaglandin analogue or beta-blocker) by the attending clinician.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known sensitivity to latanoprost or timolol eye drops
- History of breathing problems or pulmonary disease including asthma, chronic obstructive pulmonary disease
- History of heart disease involving slowed heart rate, impaired electrical conduction of the heart (i.e. sinus bradycardia, AV block) or chronic heart failure.
- Contact lens use
- Only one functional eye, poor or eccentric fixation, nystagmus
- Any corneal or conjunctival pathology or infection (keratoconus, corneal scarring, severe dry eye disease)
- History of prior incisional glaucoma surgery or cornea surgery, including corneal laser surgery
- Cataract extraction within the last two months in the study eye(s)
- Sensory or functional impairments that may limit self-handling of the ICARE HOME tonometer
- Lack of comprehension or willingness to use the tonometer as instructed

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Group 1: Allocation is not concealed

Group 2: Allocation for intervention treatment 1 or 2 will be concealed using central ransomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software, whereby even numbers will default to prostaglandin analogue, uneven number to beta-blocker in the first treatment
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Group 1: intervention treatment 1 and 2 or non-randomised as ongoing patient treatment will default to intervention treatment 1

Group 2: intervention treatment 1 and 2 will be randomised and both interventions will be administered to each patients using a crossover design
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical analysis of the data will focus on diurnal variation in IOP within and between groups and treatments. Individual patient data will be analysed using descriptive statistics including the means and standard deviations for measurement time point clustered by intervention. Data will then be grouped according to intervention to investigate the effect of medication on IOP patterns compared to no medication. Linear regression models will be employed to calculate a modified target IOP from the ICARE HOME data. One-was ANOVA will be applied to identified significant differences between groups and interventions. In addition, two-way ANOVA analysis will be used to provide information on the influence of diurnal variation and time after intervention initiation on the estimation of appropriate target IOP and therefore glaucoma management. All analyses will be performed using standard statistics software including but not limited to SPSS, Graphpad Prism and Excel.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 22972 0
2052 - Unsw Sydney
Recruitment postcode(s) [2] 22973 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 299734 0
University
Name [1] 299734 0
UNSW Sydney
Address [1] 299734 0
The University of New South Wales
Rupert Myers Building (south wing)
Barker St, Gate 14
Kensington NSW 2052
Country [1] 299734 0
Australia
Funding source category [2] 299797 0
Commercial sector/Industry
Name [2] 299797 0
Icare Finland Oy
Address [2] 299797 0
Äyritie 22 / Tuike
FI-01510 Vantaa
Country [2] 299797 0
Finland
Primary sponsor type
Individual
Name
Dr. Barbara Zangerl
Address
Centre for Eye Health
The University of New South Wales
Rupert Myers Building (south wing)
Barker St, Gate 14
Kensington NSW 2052
Country
Australia
Secondary sponsor category [1] 299069 0
University
Name [1] 299069 0
UNSW Sydney
Address [1] 299069 0
Centre for Eye Health
The University of New South Wales
Rupert Myers Building (south wing)
Barker St, Gate 14
Kensington NSW 2052
Country [1] 299069 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300624 0
The University of New South Wales Committee B
Ethics committee address [1] 300624 0
UNSW Sydney
Sydney NSW 2052
Ethics committee country [1] 300624 0
Australia
Date submitted for ethics approval [1] 300624 0
Approval date [1] 300624 0
06/06/2018
Ethics approval number [1] 300624 0
HC180186

Summary
Brief summary
Elevations and excessive fluctuations of intraocular pressure (IOP) are associated with the development and progression of glaucoma. To date, limited research has examined the effect of topical treatments on the patterns of IOP fluctuations in glaucoma patients throughout the course of the day. Access to a novel self-measurement device (Icare HOME), in addition to the research team’s experience in a completed clinical trial and access to an existing glaucoma patient cohort will allow the facilitation of a project which aims to:
• Evaluate the effect of topical glaucoma treatments (prostaglandin analogues and beta blockers) on diurnal IOP
• Identify glaucoma progression risk in patients with previously undetected, inadequate IOP control
• Provide the basis for translational research integrating rebound self-tonometry into clinical protocols for improved glaucoma patient management
Results from this study could influence clinical management protocols for glaucoma patients and suspects. Identification of diurnal IOP-related risk factors for disease progression could help clinicians manage at-risk patients appropriately to prevent irreversible vision loss.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84254 0
Dr Barbara Zangerl
Address 84254 0
The Centre for Eye Health
The University of New South Wales
Rupert Myers Building (south wing)
Barker St, Gate 14
Kensington NSW 2052
Country 84254 0
Australia
Phone 84254 0
+61 2 8118 0793
Fax 84254 0
Email 84254 0
bzangerl@cfeh.com.au
Contact person for public queries
Name 84255 0
Dr Barbara Zangerl
Address 84255 0
The Centre for Eye Health
The University of New South Wales
Rupert Myers Building (south wing)
Barker St, Gate 14
Kensington NSW 2052
Country 84255 0
Australia
Phone 84255 0
+61 2 8118 0793
Fax 84255 0
Email 84255 0
bzangerl@cfeh.com.au
Contact person for scientific queries
Name 84256 0
Dr Barbara Zangerl
Address 84256 0
The Centre for Eye Health
The University of New South Wales
Rupert Myers Building (south wing)
Barker St, Gate 14
Kensington NSW 2052
Country 84256 0
Australia
Phone 84256 0
+61 2 8118 0793
Fax 84256 0
Email 84256 0
bzangerl@cfeh.com.au

No information has been provided regarding IPD availability
Summary results
No Results