ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12616001266459

Ethics application status

Approved

Date submitted

5/09/2016

Date registered

9/09/2016

Date last updated

16/05/2019

Date data sharing statement initially provided

16/05/2019

Date results provided

16/05/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Microdrop administration of phenylephrine and cyclopentolate in neonates (MAPC-N)

Scientific title

Testing a lower than standard dose of phenylephrine and cyclopentolate in neonates requiring pupil dilation for routine retinopathy of prematurity screening and red reflex testing.

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1187-0769

Trial acronym

MAPC-N

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Retinopathy of prematurity

Condition category

Condition code

Eye

Diseases / disorders of the eye

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Participants will be randomised to receive either a combination of;
1. One combination microdrop (7 microlitre) of both phenylephrine 1% and cyclopentolate 0.2% to both eyes. Participants will have one to three doses administered depending on pupil dilation.
2. One combination microdrop (7 microlitre) of both phenylephrine 0.5% and cyclopentolate 0.1% to both eyes. Participants will have one to two doses administered depending on pupil dilation. If a third dose is required, it will be one combination microdrop (7 microlitre) of both phenylephrine 1% and cyclopentolate 0.2%

To develop an eye colour chart to determine light iris vs dark iris.

Intervention code [1]

Early detection / Screening

Comparator / control treatment

Control treatment is one combination microdrop (7 microlitre) of both phenylephrine 1% and cyclopentolate 0.2% to both eyes.

Control group

Active

Outcomes

Primary outcome [1]

To identify whether phenylephrine 1% or 0.5% and cyclopentolate 0.2% or 0.1% in a 7 microlitre volume will achieve adequate pupil dilation (>5 mm) for retinal examination in premature neonates. Pupil dilation will be measured using two pupilometers; Colvard pupilometer and a Neuroptics pupilometer.

Timepoint [1]

Pupil measurements will be taken from both eyes at baseline, 20 minute, 45 minute, 90 minute and 120 minute intervals.

Secondary outcome [1]

To describe the time-course of physiological markers of systemic absorption following eye drop administration (blood pressure).

Timepoint [1]

Blood pressure will be taken at baseline, then six hourly post mydriatic dosing for 24 hours. Manual blood pressure will be measured using a Phillips monitor.

Secondary outcome [2]

To determine if eye pigmentation (light or dark) is a potential covariate for phenylephrine and cyclopentolate induced pupil dilation.

Timepoint [2]

Pupil measurements will be taken from both eyes at baseline, 20 minute, 45 minute, 90 minute and 120 minute intervals. Pupil measurement will be measured with both a Colvard pupilometer and a Neuroptics pupilometer.

Eye pigmentation will be determined by comparing neonatal eye colour to a colour chart (dark eye colour vs light eye colour).

Secondary outcome [3]

To describe the time-course of physiological markers of systemic absorption following eye drop administration (heart rate).

Timepoint [3]

Heart rate will be continuously measured for 24 hours prior and 24 hours post eye drop installation. Heart rate will be measured using a Phillips monitor.

Secondary outcome [4]

To describe the time-course of physiological markers of systemic absorption following eye drop administration (feed intolerance).

Timepoint [4]

Feed intolerance will be reviewed by retrospectively reviewing feed volumes and spills, on either the category 4 or 5 observation chart, for 24 hours prior and 24 hours post eye drop installation. Medical notes will be reviewed for 7 days post eye drop installation to monitor for diagnosis of necrotising enterocolitis.

Eligibility

Key inclusion criteria

All neonates that meet the Dunedin Hospital, Neonatal Intensive Care Unit (NICU) retinopathy of prematurity (ROP) screening criteria.

All infants who require pupil dilation for red reflex testing.

Minimum age

6 Weeks

Maximum age

4 Months

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Any neonate with ROP greater than stage 2.
Any neonate with an ocular medical condition.
If the staff member who administered the eye drop was unsure if the microdrop reached the eye, then the neonate will be excluded from the trial, in accordance with the per-protocol study design.
Any neonate whom phenylephrine and/or cyclopentolate is contraindicated.

Study design

Purpose of the study

Diagnosis

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Sealed opaque envelopes

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Descriptive statistics for use in sample size calculations
Mean (SD) within-person dilation pre-treatment between eyes.
For those that have repeat measures: Mean (SD) within-person dilation pre-treatment, between visits for each eye.
Mean (SD) post-treatment dilation for each treatment
Mean (SD) within-person dilation post-treatment (difference between treatments). (calculated for: (a) only first visit data and (b) all data including repeats).
Pearson’s correlation coefficients for all within-person comparisons.
Proportion that sufficiently dilated for each treatment.
Range of dilation (mm) measured for “sufficient” and “not sufficient”.
Proportion of eyes/infants that had to be excluded because drop application was not successful.
Inter-observer reliability:
Inter-observer reliability assessed with intraclass correlation coefficient.
Mean (SD) difference between two measures by different observers (within-person mean. calculated, including repeats; then calculate the mean (SD) of the within-person means).
Data will be displayed visually where appropriate (histograms, scatter-plots, bar-graphs).
Statistical Analysis
Due to sample size, statistical tests in a pilot study are to be applied and interpreted with caution.
Was dilation different between treatments?
Paired and unpaired t-test for difference between treatments.
Was the proportion with sufficient dilation different between treatments?
McNemar’s test and Fishers exact test for analysis of sufficient dilation between treatments.
Was dilation different by demographics?
Using control data (current treatment) determine if pre- and post-treatment dilations are different by: gender; ethnicity; and iris colour, grade of ROP and level of respiratory support. Use unpaired t-tests for dilation measures and Fisher’s Exact test for sufficient dilation. Descriptive statistics (mean, SD and proportions) will be calculated for each of the groups.
Pupil diameter measurements
Correlations will be used for test-retest reliability of pupil diameter measurements and relative validity between measurement methods.
Ambient light measurements
Correlation between pre treatment dilation and ambient light. Difference in ambient light between those that sufficiently dilate and those that didn’t. Use unpaired t-test for analysis.
Describe the time course physiological markers
Systolic and diastolic blood pressure and heart rate results will be anaylsed using summary measures of hourly mean and peak results.
Feed intolerance will be commented on using summary measures and descriptive statements.
TEAE results will be commented on using descriptive statements.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

31/10/2016

Actual

16/01/2017

Date of last participant enrolment

Anticipated

31/03/2017

Actual

13/11/2017

Date of last data collection

Anticipated

Actual

17/12/2018

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Dunedin

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Otago

Address [1]

School of Pharmacy and Department of Medicine (Womens and Childrens)
18 Frederick St
Dunedin
9054

Country [1]

New Zealand

Primary sponsor type

University

Name

University of Otago

Address

School of Pharmacy and Department of Medicine (Womens and Childrens)
18 Frederick St
Dunedin
9054

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Hospital

Name [1]

Dunedin Hospital

Address [1]

201 Great King St
Dunedin
9054

Country [1]

New Zealand

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disability Ethics Committee

Ethics committee address [1]

Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington
6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

12/09/2016

Approval date [1]

28/11/2016

Ethics approval number [1]

16/CEN/135

Ethics committee name [2]

Health Research South

Ethics committee address [2]

Dunedin Hospital
201 Great King St
Dunedin
9054

Ethics committee country [2]

New Zealand

Date submitted for ethics approval [2]

12/09/2016

Approval date [2]

Ethics approval number [2]

Summary

Brief summary

Phenylephrine and cyclopentolate are two medicines that are currently used at Dunedin Hospital during retinopathy of prematurity screening (eye checks).  The two medicines are used to dilate the pupil so the retina can be viewed.  Both of these medicines have been associated with harmful side effects such as necrotising enterocolitis, can cause reflux, feed intolerance, increase in blood pressure (which can increase the risk of intraventricular haemorrhage), increase in heart rate and there are case reports of seizures. One of the ways side effects can be reduced, is to reduce the amount of medication administered (i.e. reduce the dose).

It is known from published papers that small doses of these two medicines are likely to be effective in dilating pupils.  What is unknown is if even smaller doses are effective, and this is what this study will compare – standard eye drop doses to half the usual dose.

The hope of the researchers, is that results from this study will suggest if using an even lower dose of phenylephrine and cyclopentolate will be effective in dilating neonatal pupils, with minimal side effects.

Trial website

n/a

Trial related presentations / publications

n/a

Public notes

n/a

Attachments [1]

/AnzctrAttachments/371442-0. MAPC-N Study Protocol.pdf (Protocol)

Attachments [2]

/AnzctrAttachments/371442-6. MAPC-N consent form.pdf (Participant information/consent)

Attachments [3]

/AnzctrAttachments/371442-5. MAPC-N Whanau Patient Information Form_V2.pdf (Participant information/consent)

Contacts

Principal investigator

Name

Miss Lisa Kremer

Address

University of Otago
School of Pharmacy
Adams Building
18 Frederick St
Dunedin
9054

Country

New Zealand

Phone

+6421973255

Fax

lisa.kremer@otago.ac.nz

Contact person for public queries

Name

Lisa Kremer

Address

University of Otago
School of Pharmacy
Adams Building
18 Frederick St
Dunedin
9054

Country

New Zealand

Phone

+6421973255

Fax

lisa.kremer@otago.ac.nz

Contact person for scientific queries

Name

Lisa Kremer

Address

University of Otago
School of Pharmacy
Adams Building
18 Frederick St
Dunedin
9054

Country

New Zealand

Phone

+6421973255

Fax

lisa.kremer@otago.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

All non-identifiable data; individual participant data underlying published results only.

When will data be available (start and end dates)?

Immediately following publication and until 31/12/2021

Available to whom?

Only researchers who provide a methodologically sound proposal, on a case-by-case basis at the discretion of this studies PI.

Available for what types of analyses?

Any purpose, only to achieve the aims in the approved proposal, for IPD meta-analyses, as deemed fit by this studies PI.

How or where can data be obtained?

Access subject to approvals by this studies Principal Investigator, requirement to sign data access agreement.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Plain language summary	No		All infants had a successful retinopathy of premat... [More Details]

Documents added automatically

No additional documents have been identified.

Trial Review

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