<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03292796</url>
  </required_header>
  <id_info>
    <org_study_id>2014OPH03L(104-0614)</org_study_id>
    <secondary_id>REC 15/EE/0239</secondary_id>
    <nct_id>NCT03292796</nct_id>
  </id_info>
  <brief_title>RCT to Investigate if Prostaglandin Analogue Drops Increase the Risk of Cystoid Macular Oedema After Cataract Surgery.</brief_title>
  <acronym>CMO</acronym>
  <official_title>A Randomised Control Study to Investigate if the Continuation of Prostaglandin Analogue Treatments in the Post-operative Phase of Glaucoma Patients Undergoing Cataract Surgery Increases the Incidence of Cystoid Macular Oedema.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Julie Dawson</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Norfolk and Norwich University Hospitals NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Post-operative cystoid macular oedema (CMO) is a common complication causing visual loss&#xD;
      following routine cataract surgery. This complication is more prevalent in eyes with&#xD;
      excessive inflammation as they heal from surgery.&#xD;
&#xD;
      Prostaglandin analogues (PGA) are the commonest first line drugs used in the long-term&#xD;
      treatment of primary open angle glaucoma (POAG)- where they reduce the pathologically high&#xD;
      pressure in the eye. Prostaglandins are inflammatory mediators.&#xD;
&#xD;
      In the post-operative care of glaucoma patients undergoing cataract surgery, there is a&#xD;
      clinical dilemma whether to stop or continue the use of prostaglandin eye drops. Clinical&#xD;
      practice is completely dichotomized between continuing and stopping PGA treatment in the&#xD;
      postoperative period. There is conflicting scientific literature on the effect of PGA on the&#xD;
      incidence of CMO; and only a single randomized control trial (Miyake K, Arch Ophthalmol 1999,&#xD;
      117:34-40), where the post operative regime is not applicable to present practice, compared&#xD;
      the incidence of CMO following routine cataract surgery in POAG on PGA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study aims to answer the common clinical question of whether or not to stop PGA after&#xD;
      routine cataract surgery. Cataract surgery is the commonest operation performed on the NHS&#xD;
      and the prevalence of glaucoma is 5% in the population over 80 years old. Thus the clinical&#xD;
      dilemma is a common one.&#xD;
&#xD;
      A current literature search reveals that a divided opinion over whether PGAs do increase the&#xD;
      incidence of CMO. No study has yet established a causal relationship between the use of PGAs&#xD;
      and the development of CMO. Anecdotal reports and small case series have associated&#xD;
      peri-operative PGA use with the occurrence of CMO (Henderson BA et al, 2007 J Cataract&#xD;
      Refract Surg 33:1550-1558; Moroi SE et al, 1999, Ophthalmology 106:1024-1029). Whilst, in&#xD;
      direct contrast, other authors argue CMO as a rare phenomenon and the causative relationship&#xD;
      is debated (Schumer RA et al 2000, Curr Opin Ophthalmol 11:94-100; Miyake K et al 2003 J&#xD;
      Cataract Refract Surg 29:1800-1810)&#xD;
&#xD;
      The most similar previous study to the one proposed, was by Miyake K et al. (Arch Ophthalmol&#xD;
      1999, 117:34-40). The key difference, though, is in the postoperative drop regime of&#xD;
      fluorometholone and diclofenac in that paper and current UK clinical practice of using&#xD;
      dexamethasone. In terms of study design, this paper used an invasive method of investigating&#xD;
      CMO by fundus fluorescein angiography compared to OCT proposed here.&#xD;
&#xD;
      A recent case report by Agange N &amp; Mosaed S (Journal of Ophthalmology, 2010) concludes with&#xD;
      'conclusions about causal relationships cannot be made without well-designed, prospective&#xD;
      clinical trials addressing this issue'.&#xD;
&#xD;
      This study will therefore use drops that are routinely used in current UK clinical practice&#xD;
      and add to the body of evidence that helps answer the question should PGAs be continued after&#xD;
      cataract surgery so as to prevent the progression of glaucoma in patients.&#xD;
&#xD;
        -  Aim&#xD;
&#xD;
             -  This study investigates if the occurrence of CMO after cataract surgery is affected&#xD;
                by the use of PGA drops by patients with glaucoma&#xD;
&#xD;
             -  The null hypothesis states there is no increase in the incidence of CMO on OCT&#xD;
                scanning in the 4 weeks following cataract surgery whether PGA eye drops continue&#xD;
                or are stopped.&#xD;
&#xD;
        -  Design&#xD;
&#xD;
             -  Randomised control study with parallel group design&#xD;
&#xD;
             -  Single masking of outcome assessors&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2016</start_date>
  <completion_date type="Actual">July 25, 2020</completion_date>
  <primary_completion_date type="Actual">October 21, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomised Control Trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The patient is not masked as to treatment group and are aware of whether they are to continue or stop the PGA drops&#xD;
The care providers are not masked as to treatment group&#xD;
Outcome assessors are masked as to the patient's treatment group for their analysis of the OCT scans over the 4 week peri-operative period.&#xD;
The scans are recorded with only the randomised identifier.&#xD;
This is to reduce bias in the analysis of the scans&#xD;
Unmasking of each patient will occur after their analysis of their week 4 OCT scan</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of cystoid macula oedema (CMO) at 4 weeks post operatively</measure>
    <time_frame>4 weeks post operatively</time_frame>
    <description>Occurrence of cystoid macula oedema (CMO) at 4 weeks post operatively.Cystoid macular oedema will be defined as an increase in the central macula thickness on the OCT with characteristic intraretinal changes in the 4 weeks following surgery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intraocular pressure (IOP) at 4 weeks post-operatively.</measure>
    <time_frame>4 weeks post operatively</time_frame>
    <description>Intraocular pressure (IOP) at 4 weeks post-operatively. Intraocular pressure will be measured by Goldmann applanation tonometry, the standard method used in clinical practice to monitor glaucoma. This forms part of the standard post-operative examination following surgery.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Open Angle Glaucoma and Cataract</condition>
  <arm_group>
    <arm_group_label>Stop prostaglandin eye drops post op</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Stop prostaglandin eye drops post operatively. Prostaglandins either stopped or continued after cataract surgery. Latanoprost Travaprost Bimatoprost Tafluprost</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continue prostaglandin eye drops post op</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Continue prostaglandin eye drops post operatively Prostaglandins either stopped or continued after cataract surgery. Latanoprost Travaprost Bimatoprost Tafluprost</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prostaglandins</intervention_name>
    <arm_group_label>Continue prostaglandin eye drops post op</arm_group_label>
    <arm_group_label>Stop prostaglandin eye drops post op</arm_group_label>
    <other_name>Latanoprost Travaprost Bimatoprost Tafluprost</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary open-angle glaucoma and ocular hypertensive subjects undergoing cataract&#xD;
             surgery (routine phacoemulsification and intraocular lens implantation) AND on current&#xD;
             topical glaucoma treatment with a prostaglandin analogue eye drop for at least 2&#xD;
             months prior to cataract surgery.&#xD;
&#xD;
          -  Subjects capable of giving informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with additional risk factors for macula oedema (eg. diabetic retinopathy,&#xD;
             previous macula oedema, uveitis)&#xD;
&#xD;
          -  Subjects with advanced glaucoma&#xD;
&#xD;
               -  Advanced visual field loss (Humphrey Mean Deviation &gt;-12dB)&#xD;
&#xD;
               -  Advanced glaucomatous disc changes (vertical cup-to-disc ratio &gt;0.9)&#xD;
&#xD;
          -  Subjects with non-controlled intraocular pressure (IOP) (pre-operative IOP &gt;22 mmHg)&#xD;
&#xD;
          -  Any contra-indication to the use of topical prostaglandin drops&#xD;
&#xD;
          -  Any contra-indication to the use of routine post-operative dexamethasone 0.1% eye&#xD;
             drops&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients unable to give informed consent&#xD;
&#xD;
          -  Intra-operative complication during cataract phacoemulsification and intraocular lens&#xD;
             implantation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nuwan Niyadurupola, Consultant</last_name>
    <role>Principal Investigator</role>
    <affiliation>Consultant Ophthalmologist</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Norfolk &amp; Norwich University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Norwich</city>
        <state>Norfolk</state>
        <zip>NR4 7UY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Agange N, Mosaed S. Prostaglandin-induced cystoid macular edema following routine cataract extraction. J Ophthalmol. 2010;2010:690707. doi: 10.1155/2010/690707. Epub 2010 Nov 7.</citation>
    <PMID>21076526</PMID>
  </reference>
  <reference>
    <citation>Henderson BA, Kim JY, Ament CS, Ferrufino-Ponce ZK, Grabowska A, Cremers SL. Clinical pseudophakic cystoid macular edema. Risk factors for development and duration after treatment. J Cataract Refract Surg. 2007 Sep;33(9):1550-8. doi: 10.1016/j.jcrs.2007.05.013.</citation>
    <PMID>17720069</PMID>
  </reference>
  <reference>
    <citation>Miyake K, Ota I, Maekubo K, Ichihashi S, Miyake S. Latanoprost accelerates disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema in early postoperative pseudophakias. Arch Ophthalmol. 1999 Jan;117(1):34-40. doi: 10.1001/archopht.117.1.34.</citation>
    <PMID>9930158</PMID>
  </reference>
  <reference>
    <citation>Miyake K, Ibaraki N, Goto Y, Oogiya S, Ishigaki J, Ota I, Miyake S. ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy. J Cataract Refract Surg. 2003 Sep;29(9):1800-10. doi: 10.1016/s0886-3350(03)00560-1.</citation>
    <PMID>14522305</PMID>
  </reference>
  <reference>
    <citation>Moroi SE, Gottfredsdottir MS, Schteingart MT, Elner SG, Lee CM, Schertzer RM, Abrams GW, Johnson MW. Cystoid macular edema associated with latanoprost therapy in a case series of patients with glaucoma and ocular hypertension. Ophthalmology. 1999 May;106(5):1024-9. doi: 10.1016/S0161-6420(99)00528-X.</citation>
    <PMID>10328408</PMID>
  </reference>
  <reference>
    <citation>Schumer RA, Camras CB, Mandahl AK. Latanoprost and cystoid macular edema: is there a causal relation? Curr Opin Ophthalmol. 2000 Apr;11(2):94-100. doi: 10.1097/00055735-200004000-00005.</citation>
    <PMID>10848227</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>October 7, 2020</last_update_submitted>
  <last_update_submitted_qc>October 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Norfolk and Norwich University Hospitals NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Julie Dawson</investigator_full_name>
    <investigator_title>Research Services Manager</investigator_title>
  </responsible_party>
  <keyword>Open Angle Glaucoma</keyword>
  <keyword>Cataract</keyword>
  <keyword>Phacoemulsification,</keyword>
  <keyword>Cystoid Macular Oedema,</keyword>
  <keyword>Prostaglandin Analogues</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</mesh_term>
    <mesh_term>Cataract</mesh_term>
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Glaucoma, Open-Angle</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bimatoprost</mesh_term>
    <mesh_term>Latanoprost</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03292796
org study id: 2014OPH03L(104-0614)
secondary id: REC 15/EE/0239
nct id: NCT03292796
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Post-operative cystoid macular oedema (CMO) is a common complication causing visual loss
      following routine cataract surgery. This complication is more prevalent in eyes with
      excessive inflammation as they heal from surgery.

      Prostaglandin analogues (PGA) are the commonest first line drugs used in the long-term
      treatment of primary open angle glaucoma (POAG)- where they reduce the pathologically high
      pressure in the eye. Prostaglandins are inflammatory mediators.

      In the post-operative care of glaucoma patients undergoing cataract surgery, there is a
      clinical dilemma whether to stop or continue the use of prostaglandin eye drops. Clinical
      practice is completely dichotomized between continuing and stopping PGA treatment in the
      postoperative period. There is conflicting scientific literature on the effect of PGA on the
      incidence of CMO; and only a single randomized control trial (Miyake K, Arch Ophthalmol 1999,
      117:34-40), where the post operative regime is not applicable to present practice, compared
      the incidence of CMO following routine cataract surgery in POAG on PGA.
This study aims to answer the common clinical question of whether or not to stop PGA after
      routine cataract surgery. Cataract surgery is the commonest operation performed on the NHS
      and the prevalence of glaucoma is 5% in the population over 80 years old. Thus the clinical
      dilemma is a common one.

      A current literature search reveals that a divided opinion over whether PGAs do increase the
      incidence of CMO. No study has yet established a causal relationship between the use of PGAs
      and the development of CMO. Anecdotal reports and small case series have associated
      peri-operative PGA use with the occurrence of CMO (Henderson BA et al, 2007 J Cataract
      Refract Surg 33:1550-1558; Moroi SE et al, 1999, Ophthalmology 106:1024-1029). Whilst, in
      direct contrast, other authors argue CMO as a rare phenomenon and the causative relationship
      is debated (Schumer RA et al 2000, Curr Opin Ophthalmol 11:94-100; Miyake K et al 2003 J
      Cataract Refract Surg 29:1800-1810)

      The most similar previous study to the one proposed, was by Miyake K et al. (Arch Ophthalmol
      1999, 117:34-40). The key difference, though, is in the postoperative drop regime of
      fluorometholone and diclofenac in that paper and current UK clinical practice of using
      dexamethasone. In terms of study design, this paper used an invasive method of investigating
      CMO by fundus fluorescein angiography compared to OCT proposed here.

      A recent case report by Agange N & Mosaed S (Journal of Ophthalmology, 2010) concludes with
      'conclusions about causal relationships cannot be made without well-designed, prospective
      clinical trials addressing this issue'.

      This study will therefore use drops that are routinely used in current UK clinical practice
      and add to the body of evidence that helps answer the question should PGAs be continued after
      cataract surgery so as to prevent the progression of glaucoma in patients.

        -  Aim

             -  This study investigates if the occurrence of CMO after cataract surgery is affected
                by the use of PGA drops by patients with glaucoma

             -  The null hypothesis states there is no increase in the incidence of CMO on OCT
                scanning in the 4 weeks following cataract surgery whether PGA eye drops continue
                or are stopped.

        -  Design

             -  Randomised control study with parallel group design

             -  Single masking of outcome assessors
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised Control Trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The patient is not masked as to treatment group and are aware of whether they are to continue or stop the PGA drops
The care providers are not masked as to treatment group
Outcome assessors are masked as to the patient's treatment group for their analysis of the OCT scans over the 4 week peri-operative period.
The scans are recorded with only the randomised identifier.
This is to reduce bias in the analysis of the scans
Unmasking of each patient will occur after their analysis of their week 4 OCT scan
measure: Occurrence of cystoid macula oedema (CMO) at 4 weeks post operatively
time frame: 4 weeks post operatively
description: Occurrence of cystoid macula oedema (CMO) at 4 weeks post operatively.Cystoid macular oedema will be defined as an increase in the central macula thickness on the OCT with characteristic intraretinal changes in the 4 weeks following surgery.
measure: Intraocular pressure (IOP) at 4 weeks post-operatively.
time frame: 4 weeks post operatively
description: Intraocular pressure (IOP) at 4 weeks post-operatively. Intraocular pressure will be measured by Goldmann applanation tonometry, the standard method used in clinical practice to monitor glaucoma. This forms part of the standard post-operative examination following surgery.
arm group label: Stop prostaglandin eye drops post op
arm group type: Other
description: Stop prostaglandin eye drops post operatively. Prostaglandins either stopped or continued after cataract surgery. Latanoprost Travaprost Bimatoprost Tafluprost
arm group label: Continue prostaglandin eye drops post op
arm group type: Other
description: Continue prostaglandin eye drops post operatively Prostaglandins either stopped or continued after cataract surgery. Latanoprost Travaprost Bimatoprost Tafluprost
intervention type: Drug
intervention name: Prostaglandins
arm group label: Continue prostaglandin eye drops post op
arm group label: Stop prostaglandin eye drops post op
other name: Latanoprost Travaprost Bimatoprost Tafluprost
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Nuwan Niyadurupola, Consultant
role: Principal Investigator
affiliation: Consultant Ophthalmologist
facility: 
country: United Kingdom
citation: Agange N, Mosaed S. Prostaglandin-induced cystoid macular edema following routine cataract extraction. J Ophthalmol. 2010;2010:690707. doi: 10.1155/2010/690707. Epub 2010 Nov 7.
PMID: 21076526
citation: Henderson BA, Kim JY, Ament CS, Ferrufino-Ponce ZK, Grabowska A, Cremers SL. Clinical pseudophakic cystoid macular edema. Risk factors for development and duration after treatment. J Cataract Refract Surg. 2007 Sep;33(9):1550-8. doi: 10.1016/j.jcrs.2007.05.013.
PMID: 17720069
citation: Miyake K, Ota I, Maekubo K, Ichihashi S, Miyake S. Latanoprost accelerates disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema in early postoperative pseudophakias. Arch Ophthalmol. 1999 Jan;117(1):34-40. doi: 10.1001/archopht.117.1.34.
PMID: 9930158
citation: Miyake K, Ibaraki N, Goto Y, Oogiya S, Ishigaki J, Ota I, Miyake S. ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy. J Cataract Refract Surg. 2003 Sep;29(9):1800-10. doi: 10.1016/s0886-3350(03)00560-1.
PMID: 14522305
citation: Moroi SE, Gottfredsdottir MS, Schteingart MT, Elner SG, Lee CM, Schertzer RM, Abrams GW, Johnson MW. Cystoid macular edema associated with latanoprost therapy in a case series of patients with glaucoma and ocular hypertension. Ophthalmology. 1999 May;106(5):1024-9. doi: 10.1016/S0161-6420(99)00528-X.
PMID: 10328408
citation: Schumer RA, Camras CB, Mandahl AK. Latanoprost and cystoid macular edema: is there a causal relation? Curr Opin Ophthalmol. 2000 Apr;11(2):94-100. doi: 10.1097/00055735-200004000-00005.
PMID: 10848227
responsible party type: Sponsor-Investigator
investigator affiliation: Norfolk and Norwich University Hospitals NHS Foundation Trust
investigator full name: Julie Dawson
investigator title: Research Services Manager
mesh term: Glaucoma
mesh term: Cataract
mesh term: Macular Edema
mesh term: Glaucoma, Open-Angle
mesh term: Bimatoprost
mesh term: Latanoprost
sharing ipd: Undecided