Comparison of Epinephrine and Phenylephrine/Ketorolac With Regards to Pupil Size

Sponsor
Milton S. Hershey Medical Center (Other)
Overall Status
Terminated
CT.gov ID
NCT02895035
Collaborator
(none)
59
Enrollment
2
Arms
28
Actual Duration (Months)

Study Details

Study Description

Brief Summary

The objective of this study is to compare the maintenance of intraoperative mydriasis during cataract surgery between two drugs: epinephrine, which has routinely been used for decades, and Omidria, a newly FDA approved combination drug of phenylephrine and ketorolac. Patients undergoing cataract surgery that are enrolled in the trial will randomly receive one of the drugs in one eye, and the other eye will receive the drug during the subsequent cataract surgery.

Condition or DiseaseIntervention/TreatmentPhase
Phase 4

Detailed Description

Cataract remains a leading cause of correctable blindness worldwide. Over 3.5 million cataract surgeries in the United States and 20 million cataract surgeries worldwide are performed every year. Cataract surgery is performed by making a small incision, removing the cataractous lens, most often through the process of phacoemulsification, and replacement with an intraocular lens. Like all surgeries, adequate exposure and field of view is vital for a safe and effective surgery. In cataract surgery, the field of view is limited by the diameter of the pupil. Several different drugs, such as cyclopentolate, tropicamide, phenylephrine, and epinephrine are utilized to maintain dilation (mydriasis) of the pupil during surgery.

There are currently two prospective randomized controlled trials comparing phenylephrine/ketorolac to placebo in the published literature. Both of these studies demonstrated that phenylephrine/ketorolac is superior to placebo for the maintenance of mydriasis during cataract surgery. Epinephrine has been the standard of care for intraoperative mydriasis. Phenylephrine/ketorolac (Omidria) is a newly FDA-approved additive for the maintenance of intraoperative mydriasis, but there are currently no published studies comparing epinephrine to phenylephrine/ketorolac for maintenance of mydriasis during cataract surgery.

While both of these drugs have been shown to be superior to placebo for the maintenance of mydriasis, there is a significant cost difference between epinephrine, which has been used for many years, and phenylephrine/ketorolac, which gained FDA approval in 2014. One 4 mL vial of Omidria® is utilized for one cataract surgery, which costs $465.

The primary endpoint to be measured in the study is the mean area under the curve change from baseline in pupil diameter over time to the end of cataract surgery.

Secondary endpoints will be maximum intraoperative pupil constriction, subjects with pupil diameter less than 6.5 mm at any during surgery, subjects with pupil less than 6.0 mm during cortical clean-up, and subjects with greater than 2.5 mm of pupillary constriction at any time during surgery.

Study Design

Study Type:
Interventional
Actual Enrollment :
59 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
Prospective Comparison of Epinephrine and Phenylephrine/Ketorolac (Omidria®) Additives With Regards to Intraoperative Pupil Size
Actual Study Start Date :
Sep 1, 2016
Actual Primary Completion Date :
Dec 31, 2018
Actual Study Completion Date :
Dec 31, 2018

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Epinephrine

Epinephrine is the intracameral additive during cataract surgery.

Drug: Epinephrine
Epinephrine is a nonselective adrenergic agonist added to the irrigation solution during cataract surgery.

Active Comparator: Omidria

Omidria is the intracameral additive during cataract surgery.

Drug: Phenylephrine-ketorolac
Pehnylephrine-ketorolac is a combination of an alpha-one agonist (phenylephrine) and an NSAID (ketorolac). One 4-mL bottle of 1% phenylephrine/3% ketorolac is added to the irrigation solution during cataract surgery.
Other Names:
  • Omidria
  • Outcome Measures

    Primary Outcome Measures

    1. Mean Area Under the Curve Change From Baseline in Pupil Diameter Over Time to the End of Cataract Surgery [During cataract surgery, with maximum end time of 20 minutes]

      Mean area under the curve was calculated by assessing the pupil diameter at baseline and then again at 1 minute intervals until the surgery was complete (max 20 minutes). Units are in millimeters*seconds

    Secondary Outcome Measures

    1. Maximum Intraoperative Change in Pupil Diameter [During cataract surgery, with maximum end time of 20 minutes]

      This is the maximum observed change in pupil diameter, as measured compared to baseline.

    2. Number of Eyes With Pupil Diameter Less Than 6 mm at Any Time During Surgery [During cataract surgery, with maximum end time of 20 minutes]

      Number of eyes with a measured pupil diameter less than 6 mm at any time during surgery

    3. Number of Eyes With Pupil Diameter Less Than 6 mm During Cortical Clean-up [During cataract surgery, cortical clean-up stage, up to 5 mins]

      Number of eyes with a measured pupil diameter less than 6 mm during cortical clean-up

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients who are older than 18 years of age

    • Patients who are planned to undergo bilateral cataract surgery

    • Patients with baseline IOP of 5 - 22 mm Hg

    • Medicare insurance*

    • There is a significant cost difference between our two study drugs. Therefore, Medicare insurance is part of our inclusion criteria, because there is a pass-through reimbursement in place to cover the cost of phenylephrine/ketorolac. Other insurances (for example, Aetna Better Health, Highmark Freedom, Gateway) have variable or poor coverage for phenylephrine/ketorolac, which would leave the medical center responsible for the cost. Patients can never be held responsible for the cost of the medication because it is included in "covered services" for cataract surgery billing.

    Exclusion Criteria:
    • Patients who are planned to undergo only unilateral cataract surgery

    • Patients who are planned to undergo cataract surgery and another surgical procedure in the same operation (eg. combined cataract and glaucoma surgery)

    • Patients with concurrent clinically significant disease, connective tissue disease, abnormal blood pressure at screening, narrow-angle or unstable glaucoma or treatment with prostaglandins, uncontrolled chronic eye disease or active corneal pathology or scarring

    • Patients with history of iritis or trauma with iris damage

    • Patients with recent eye surgery (non-laser surgery within 3 months or laser surgery within 30 days prior to study surgery)

    • Patients with clinically significant hypersensitivity to the study medications

    • Patients who have used pilocarpine (a pupil constrictor) within 6 months prior to surgery

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Milton S. Hershey Medical Center

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Seth M Pantanelli, Principal Investigator, Milton S. Hershey Medical Center
    ClinicalTrials.gov Identifier:
    NCT02895035
    Other Study ID Numbers:
    • 00005630
    First Posted:
    Sep 9, 2016
    Last Update Posted:
    Jan 31, 2020
    Last Verified:
    Jan 1, 2020

    Study Results

    Participant Flow

    Recruitment DetailsAll patients who presented to one of two attending ophthalmologist's (MCC or SMP) clinics at Penn State Eye Center for cataract evaluation between November 10, 2016 and February 8, 2018 and met inclusion/exclusion criteria were invited to participate in the study. There were no incentives provided to patients for enrolling in the study.
    Pre-assignment Detail
    Arm/Group TitleEpinephrine (1 Day), Washout (21 Days), Then Omidria (1 Day)Omidria (1 Day), Washout (21 Days), Then Epinephrine (1 Day)
    Arm/Group DescriptionPatients in this arm received epinephrine during the first eye surgery. Patients then waited (washout) 21 days before proceeding with second eye surgery. Patients then received Omidria during the second eye surgery.Patients in this arm received Omidria during the first eye surgery. Patients then waited (washout) 21 days before proceeding with second eye surgery. Patients then received epinephrine during the second eye surgery.
    Period Title: Overall Study
    STARTED2336
    COMPLETED1824
    NOT COMPLETED512

    Baseline Characteristics

    Arm/Group TitleAll Participants
    Arm/Group DescriptionAll Participants were randomized to receive all interventions. Therefore, the baseline characteristics are grouped as "all participants"
    Overall Participants42
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    73.1
    (7.1)
    Sex: Female, Male (Count of Participants)
    Female
    36
    85.7%
    Male
    6
    14.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    40
    95.2%
    Not Hispanic or Latino
    2
    4.8%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    42
    100%
    Tamsulosin Use (Count of Participants)
    Tamsulosin
    1
    2.4%
    No Tamsulosin
    41
    97.6%

    Outcome Measures

    1. Primary Outcome
    TitleMean Area Under the Curve Change From Baseline in Pupil Diameter Over Time to the End of Cataract Surgery
    DescriptionMean area under the curve was calculated by assessing the pupil diameter at baseline and then again at 1 minute intervals until the surgery was complete (max 20 minutes). Units are in millimeters*seconds
    Time FrameDuring cataract surgery, with maximum end time of 20 minutes

    Outcome Measure Data

    Analysis Population Description
    Two eyes from each participant were included for all outcome measures.
    Arm/Group TitleEpinephrineOmidria
    Arm/Group DescriptionEpinephrine is the intracameral additive during cataract surgery. Epinephrine: Epinephrine is a nonselective adrenergic agonist added to the irrigation solution during cataract surgery.Omidria is the intracameral additive during cataract surgery. Phenylephrine-ketorolac: Pehnylephrine-ketorolac is a combination of an alpha-one agonist (phenylephrine) and an NSAID (ketorolac). One 4-mL bottle of 1% phenylephrine/3% ketorolac is added to the irrigation solution during cataract surgery.
    Measure Participants4242
    Measure Eyes4242
    Mean (Standard Deviation) [millimeters * seconds]
    1.76
    (6.51)
    0.8
    (12.01)
    2. Secondary Outcome
    TitleMaximum Intraoperative Change in Pupil Diameter
    DescriptionThis is the maximum observed change in pupil diameter, as measured compared to baseline.
    Time FrameDuring cataract surgery, with maximum end time of 20 minutes

    Outcome Measure Data

    Analysis Population Description
    Two eyes from each participant were included
    Arm/Group TitleEpinephrineOmidria
    Arm/Group DescriptionEpinephrine is the intracameral additive during cataract surgery. Epinephrine: Epinephrine is a nonselective adrenergic agonist added to the irrigation solution during cataract surgery.Omidria is the intracameral additive during cataract surgery. Phenylephrine-ketorolac: Pehnylephrine-ketorolac is a combination of an alpha-one agonist (phenylephrine) and an NSAID (ketorolac). One 4-mL bottle of 1% phenylephrine/3% ketorolac is added to the irrigation solution during cataract surgery.
    Measure Participants4242
    Measure Eyes4242
    Mean (Standard Deviation) [millimeters]
    -0.71
    (0.57)
    -0.66
    (0.79)
    3. Secondary Outcome
    TitleNumber of Eyes With Pupil Diameter Less Than 6 mm at Any Time During Surgery
    DescriptionNumber of eyes with a measured pupil diameter less than 6 mm at any time during surgery
    Time FrameDuring cataract surgery, with maximum end time of 20 minutes

    Outcome Measure Data

    Analysis Population Description
    Each participant had two eyes included in the study
    Arm/Group TitleEpinephrineOmidria
    Arm/Group DescriptionEpinephrine is the intracameral additive during cataract surgery. Epinephrine: Epinephrine is a nonselective adrenergic agonist added to the irrigation solution during cataract surgery.Omidria is the intracameral additive during cataract surgery. Phenylephrine-ketorolac: Pehnylephrine-ketorolac is a combination of an alpha-one agonist (phenylephrine) and an NSAID (ketorolac). One 4-mL bottle of 1% phenylephrine/3% ketorolac is added to the irrigation solution during cataract surgery.
    Measure Participants4242
    Measure Eyes4242
    Count of Units [Eyes]
    3
    2
    4. Secondary Outcome
    TitleNumber of Eyes With Pupil Diameter Less Than 6 mm During Cortical Clean-up
    DescriptionNumber of eyes with a measured pupil diameter less than 6 mm during cortical clean-up
    Time FrameDuring cataract surgery, cortical clean-up stage, up to 5 mins

    Outcome Measure Data

    Analysis Population Description
    Each participant had two eyes included in the study
    Arm/Group TitleEpinephrineOmidria
    Arm/Group DescriptionEpinephrine is the intracameral additive during cataract surgery. Epinephrine: Epinephrine is a nonselective adrenergic agonist added to the irrigation solution during cataract surgery.Omidria is the intracameral additive during cataract surgery. Phenylephrine-ketorolac: Pehnylephrine-ketorolac is a combination of an alpha-one agonist (phenylephrine) and an NSAID (ketorolac). One 4-mL bottle of 1% phenylephrine/3% ketorolac is added to the irrigation solution during cataract surgery.
    Measure Participants4242
    Measure Eyes4242
    Count of Units [Eyes]
    3
    2

    Adverse Events

    Time Frame
    Adverse Event Reporting Description All-Cause Mortality, Serious, and Other [Not Including Serious] Adverse Events were not monitored/assessed.
    Arm/Group TitleEpinephrineOmidria
    Arm/Group DescriptionEpinephrine is the intracameral additive during cataract surgery. Epinephrine: Epinephrine is a nonselective adrenergic agonist added to the irrigation solution during cataract surgery.Omidria is the intracameral additive during cataract surgery. Phenylephrine-ketorolac: Pehnylephrine-ketorolac is a combination of an alpha-one agonist (phenylephrine) and an NSAID (ketorolac). One 4-mL bottle of 1% phenylephrine/3% ketorolac is added to the irrigation solution during cataract surgery.
    All Cause Mortality
    EpinephrineOmidria
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/0 (NaN) 0/0 (NaN)
    Serious Adverse Events
    EpinephrineOmidria
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/0 (NaN) 0/0 (NaN)
    Other (Not Including Serious) Adverse Events
    EpinephrineOmidria
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/0 (NaN) 0/0 (NaN)

    Limitations/Caveats

    small sample size some patients received pre-operative topical NSAID in both eyes, while others did not

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleSeth Pantanelli
    OrganizationPenn State Hershey Eye Center
    Phone717-531-5690
    Emailspantanelli@pennstatehealth.psu.edu
    Responsible Party:
    Seth M Pantanelli, Principal Investigator, Milton S. Hershey Medical Center
    ClinicalTrials.gov Identifier:
    NCT02895035
    Other Study ID Numbers:
    • 00005630
    First Posted:
    Sep 9, 2016
    Last Update Posted:
    Jan 31, 2020
    Last Verified:
    Jan 1, 2020