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Ocular Hypertension Treatment Study (OHTS) (OHTS)

Primary Purpose

Ocular Hypertension, Glaucoma

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Topical ocular hypotensive eye drops.
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ocular Hypertension

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Men and nonpregnant women between the ages of 40 and 80 with IOP greater than or equal to 24 mm Hg but less than or equal to 32 mm Hg in at least one eye and IOP greater than or equal to 21 but less than or equal to 32 mm Hg in the fellow eye, as well as normal visual fields and optic discs are eligible for the trial. Patients presenting with best-corrected visual acuity worse than 20/40 in either eye, previous intraocular surgery, a life-threatening or debilitating disease, secondary causes of elevated IOP, angle-closure glaucoma or anatomically narrow angles, other diseases that can cause visual field loss, background diabetic retinopathy, optic disc abnormalities that can produce visual field loss or obscure the interpretation of the optic disc, or unwillingness to undergo random assignment are excluded from the trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    No Intervention

    Other

    Arm Label

    Observation

    Treatment

    Arm Description

    Close Observation.

    Participants treated with commercially available topical ocular hypotensive eye drops.

    Outcomes

    Primary Outcome Measures

    Incidence of Primary Open-Angle Glaucoma in Hypotensive Patients
    Comparison of the cumulative proportion of participants who develop primary open-angle glaucoma in the observation and medication groups.

    Secondary Outcome Measures

    Full Information

    First Posted
    September 23, 1999
    Last Updated
    May 20, 2020
    Sponsor
    Washington University School of Medicine
    Collaborators
    National Eye Institute (NEI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00000125
    Brief Title
    Ocular Hypertension Treatment Study (OHTS)
    Acronym
    OHTS
    Official Title
    Ocular Hypertension Treatment Study (OHTS)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    February 1994 (Actual)
    Primary Completion Date
    June 2002 (Actual)
    Study Completion Date
    June 30, 2019 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Washington University School of Medicine
    Collaborators
    National Eye Institute (NEI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    To determine whether medical reduction of intraocular pressure prevents or delays the onset of glaucomatous visual field loss and/or optic disc damage in ocular hypertensive participants judged to be at moderate risk for developing open-angle glaucoma. To produce natural history data to assist in identifying patients at most risk for developing open-angle glaucoma and those most likely to benefit from early medical treatment. To quantify risk factors for developing open-angle glaucoma among ocular hypertensive individuals.
    Detailed Description
    OHTS Phase 3 will re-examine study participants 20 plus years after enrollment to document clinical status and the incidence and severity of self-reported functional limitations. The 279 participants who developed POAG in OHTS Phase 1 or 2 will have more than 10 years of post-POAG follow-up by Phase 3. The timing of re-examination at 20 years is meaningful because 20 years approaches the median life expectancy of OHT patients in their 60's and 70's and half the median life expectancy of patients in their 40's and 50's. For the first time, patients with ocular hypertension and clinicians will have high quality data about the long-term risk of developing POAG and functional limitations associated with the disease. These data will facilitate patient-centered care so that patients and clinicians can decide on the appropriate frequency of tests and examinations and the potential benefit of preventative treatment. Glaucoma is one of the leading causes of blindness in the United States and other industrialized countries. It is estimated that 2 million people in the United States have glaucoma and that 80,000 of these individuals are legally blind from the disease. Among African Americans, glaucoma is now recognized as the leading cause of blindness. Elevated intraocular pressure (IOP), a common condition affecting 3 to 6 million people in the United States, is thought to be the leading risk factor for development of open-angle glaucoma. There is no consensus that medical reduction of intraocular pressure prevents or delays the onset of visual field and/or optic nerve damage in ocular hypertensive subjects. Despite the lack of convincing evidence for the efficacy of medical treatment in ocular hypertension, approximately 1.5 million glaucoma suspects in the United States are being treated with costly ocular hypotensive medications that carry the potential for serious and even life-threatening side effects. Clearly, there is a need for a well-controlled clinical trial to determine whether medical reduction of IOP can prevent or delay the onset of glaucomatous damage in ocular hypertensive subjects. Only then can clinicians and patients make rational choices and health care planners ensure that limited medical resources are being allocated in a safe and cost-effective manner. The Ocular Hypertension Treatment Study (OHTS) is a long-term, randomized, controlled multicenter clinical trial. Ocular hypertensive subjects judged to be at moderate risk of developing primary open-angle glaucoma are randomly assigned to either close observation only or a stepped medical regimen. Medical treatment consists of all commercially available topical ocular hypotensive eye drops. After completion of baseline measures (IOP, visual fields, disc photos) and randomization, the subjects are followed for a minimum of 5 years with automated threshold central static perimetry (Humphrey program 30-2) twice yearly and stereoscopic optic disc photographs once yearly. Study end points are reproducible visual field loss and/or progressive optic disc damage in either eye of a patient attributed to glaucoma by a Masked Endpoint Committee. All visual fields and optic disc photographs are read in a masked fashion in Reading Centers. In the 1991 Baltimore Eye Survey, African Americans were shown to have a prevalence of open-angle glaucoma four to five times higher than whites. Given this high prevalence of glaucoma in the African American population, it is important to recruit and follow an adequate sample of African American subjects in the trial (approximately 25 percent of the total patient sample). At the conclusion of this study, practitioners should be able to make reasonable estimates of risk for individual ocular hypertensive patients and to determine which ocular hypertensive individuals are most likely to benefit from early prophylactic medical treatment.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ocular Hypertension, Glaucoma

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    1636 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Observation
    Arm Type
    No Intervention
    Arm Description
    Close Observation.
    Arm Title
    Treatment
    Arm Type
    Other
    Arm Description
    Participants treated with commercially available topical ocular hypotensive eye drops.
    Intervention Type
    Drug
    Intervention Name(s)
    Topical ocular hypotensive eye drops.
    Intervention Description
    Topical ocular hypotensive eye drops.
    Primary Outcome Measure Information:
    Title
    Incidence of Primary Open-Angle Glaucoma in Hypotensive Patients
    Description
    Comparison of the cumulative proportion of participants who develop primary open-angle glaucoma in the observation and medication groups.
    Time Frame
    5 yrs (OHTS I, June 2002) and 13.0 yrs (completion of both phases of OHTS, March 2009)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Men and nonpregnant women between the ages of 40 and 80 with IOP greater than or equal to 24 mm Hg but less than or equal to 32 mm Hg in at least one eye and IOP greater than or equal to 21 but less than or equal to 32 mm Hg in the fellow eye, as well as normal visual fields and optic discs are eligible for the trial. Patients presenting with best-corrected visual acuity worse than 20/40 in either eye, previous intraocular surgery, a life-threatening or debilitating disease, secondary causes of elevated IOP, angle-closure glaucoma or anatomically narrow angles, other diseases that can cause visual field loss, background diabetic retinopathy, optic disc abnormalities that can produce visual field loss or obscure the interpretation of the optic disc, or unwillingness to undergo random assignment are excluded from the trial.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Michael A Kass, MD
    Organizational Affiliation
    Washington University Department of Ophthalmology and Visual Sciences
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    10326953
    Citation
    Gordon MO, Kass MA. The Ocular Hypertension Treatment Study: design and baseline description of the participants. Arch Ophthalmol. 1999 May;117(5):573-83. doi: 10.1001/archopht.117.5.573.
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    PubMed Identifier
    10980763
    Citation
    Keltner JL, Johnson CA, Quigg JM, Cello KE, Kass MA, Gordon MO. Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study. Ocular Hypertension Treatment Study Group. Arch Ophthalmol. 2000 Sep;118(9):1187-94. doi: 10.1001/archopht.118.9.1187.
    Results Reference
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    PubMed Identifier
    11024416
    Citation
    Piltz J, Gross R, Shin DH, Beiser JA, Dorr DA, Kass MA, Gordon MO. Contralateral effect of topical beta-adrenergic antagonists in initial one-eyed trials in the ocular hypertension treatment study. Am J Ophthalmol. 2000 Oct;130(4):441-53. doi: 10.1016/s0002-9394(00)00527-4.
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    PubMed Identifier
    11581049
    Citation
    Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001 Oct;108(10):1779-88. doi: 10.1016/s0161-6420(01)00760-6.
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    PubMed Identifier
    11755836
    Citation
    Feuer WJ, Parrish RK 2nd, Schiffman JC, Anderson DR, Budenz DL, Wells MC, Hess DJ, Kass MA, Gordon MO. The Ocular Hypertension Treatment Study: reproducibility of cup/disk ratio measurements over time at an optic disc reading center. Am J Ophthalmol. 2002 Jan;133(1):19-28. doi: 10.1016/s0002-9394(01)01338-1.
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    PubMed Identifier
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    Citation
    Johnson CA, Keltner JL, Cello KE, Edwards M, Kass MA, Gordon MO, Budenz DL, Gaasterland DE, Werner E; Ocular Hypertension Study Group. Baseline visual field characteristics in the ocular hypertension treatment study. Ophthalmology. 2002 Mar;109(3):432-7. doi: 10.1016/s0161-6420(01)00948-4.
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    Citation
    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.
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    Citation
    Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Kass MA. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002 Jun;120(6):714-20; discussion 829-30. doi: 10.1001/archopht.120.6.714.
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    Keltner JL, Johnson CA, Cello KE, Edwards MA, Bandermann SE, Kass MA, Gordon MO; Ocular Hypertension Treatment Study Group. Classification of visual field abnormalities in the ocular hypertension treatment study. Arch Ophthalmol. 2003 May;121(5):643-50. doi: 10.1001/archopht.121.5.643. Erratum In: Arch Ophthalmol. 2008 Apr;126(4):561.
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    Zangwill LM, Weinreb RN, Berry CC, Smith AR, Dirkes KA, Coleman AL, Piltz-Seymour JR, Liebmann JM, Cioffi GA, Trick G, Brandt JD, Gordon MO, Kass MA; Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study. Racial differences in optic disc topography: baseline results from the confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study. Arch Ophthalmol. 2004 Jan;122(1):22-8. doi: 10.1001/archopht.122.1.22.
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    Higginbotham EJ, Gordon MO, Beiser JA, Drake MV, Bennett GR, Wilson MR, Kass MA; Ocular Hypertension Treatment Study Group. The Ocular Hypertension Treatment Study: topical medication delays or prevents primary open-angle glaucoma in African American individuals. Arch Ophthalmol. 2004 Jun;122(6):813-20. doi: 10.1001/archopht.122.6.813.
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    Coleman AL, Gordon MO, Beiser JA, Kass MA; Ocular Hypertension Treatment Study. Baseline risk factors for the development of primary open-angle glaucoma in the Ocular Hypertension Treatment Study. Am J Ophthalmol. 2004 Oct;138(4):684-5. doi: 10.1016/j.ajo.2004.05.030.
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    Brandt JD, Beiser JA, Gordon MO, Kass MA; Ocular Hypertension Treatment Study (OHTS) Group. Central corneal thickness and measured IOP response to topical ocular hypotensive medication in the Ocular Hypertension Treatment Study. Am J Ophthalmol. 2004 Nov;138(5):717-22. doi: 10.1016/j.ajo.2004.07.036.
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    Citation
    Kass MA, Gordon MO, Kymes SM. Incorporating the results of the Ocular Hypertension Treatment Study into clinical practice. Arch Ophthalmol. 2005 Jul;123(7):1021-2. doi: 10.1001/archopht.123.7.1021-b. No abstract available.
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    Keltner JL, Johnson CA, Levine RA, Fan J, Cello KE, Kass MA, Gordon MO. Normal visual field test results following glaucomatous visual field end points in the Ocular Hypertension Treatment Study. Arch Ophthalmol. 2005 Sep;123(9):1201-6. doi: 10.1001/archopht.123.9.1201.
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    Budenz DL, Anderson DR, Feuer WJ, Beiser JA, Schiffman J, Parrish RK 2nd, Piltz-Seymour JR, Gordon MO, Kass MA; Ocular Hypertension Treatment Study Group. Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study. Ophthalmology. 2006 Dec;113(12):2137-43. doi: 10.1016/j.ophtha.2006.06.022. Epub 2006 Sep 25.
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    Bhorade AM, Gordon MO, Wilson B, Weinreb RN, Kass MA; Ocular Hypertension Treatment Study Group. Variability of intraocular pressure measurements in observation participants in the ocular hypertension treatment study. Ophthalmology. 2009 Apr;116(4):717-24. doi: 10.1016/j.ophtha.2008.12.036. Epub 2009 Feb 25. Erratum In: Ophthalmology. 2009 May;116(5):822. Weinrab, Robert N [corrected to Weinreb, Robert N].
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    Barnett EM, Fantin A, Wilson BS, Kass MA, Gordon MO; Ocular Hypertension Treatment Study Group. The incidence of retinal vein occlusion in the ocular hypertension treatment study. Ophthalmology. 2010 Mar;117(3):484-8. doi: 10.1016/j.ophtha.2009.08.022. Epub 2010 Jan 19.
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    Kymes SM, Plotzke MR, Kass MA, Boland MV, Gordon MO. Effect of patient's life expectancy on the cost-effectiveness of treatment for ocular hypertension. Arch Ophthalmol. 2010 May;128(5):613-8. doi: 10.1001/archophthalmol.2010.83.
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    Weinreb RN, Zangwill LM, Jain S, Becerra LM, Dirkes K, Piltz-Seymour JR, Cioffi GA, Trick GL, Coleman AL, Brandt JD, Liebmann JM, Gordon MO, Kass MA; OHTS CSLO Ancillary Study Group. Predicting the onset of glaucoma: the confocal scanning laser ophthalmoscopy ancillary study to theOcular Hypertension Treatment Study. Ophthalmology. 2010 Sep;117(9):1674-83. doi: 10.1016/j.ophtha.2010.03.044. Epub 2010 Jul 14.
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    Bhorade AM, Wilson BS, Gordon MO, Palmberg P, Weinreb RN, Miller E, Chang RT, Kass MA; Ocular Hypertension Treatment Study Group. The utility of the monocular trial: data from the ocular hypertension treatment study. Ophthalmology. 2010 Nov;117(11):2047-54. doi: 10.1016/j.ophtha.2010.02.020. Epub 2010 Aug 12.
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    Artes PH, Chauhan BC, Keltner JL, Cello KE, Johnson CA, Anderson DR, Gordon MO, Kass MA; Ocular Hypertension Treatment Study Group. Longitudinal and cross-sectional analyses of visual field progression in participants of the Ocular Hypertension Treatment Study. Arch Ophthalmol. 2010 Dec;128(12):1528-32. doi: 10.1001/archophthalmol.2010.292.
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    Gao F, Miller JP, Xiong C, Beiser JA, Gordon M; The Ocular Hypertension Treatment Study (OHTS) Group. A joint-modeling approach to assess the impact of biomarker variability on the risk of developing clinical outcome. Stat Methods Appt. 2011 Mar 1;20(1):83-100. doi: 10.1007/s10260-010-0150-z.
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    Gordon MO, Gao F, Beiser JA, Miller JP, Kass MA. The 10-year incidence of glaucoma among patients with treated and untreated ocular hypertension. Arch Ophthalmol. 2011 Dec;129(12):1630-1. doi: 10.1001/archophthalmol.2011.337. No abstract available.
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    Demirel S, De Moraes CG, Gardiner SK, Liebmann JM, Cioffi GA, Ritch R, Gordon MO, Kass MA; Ocular Hypertension Treatment Study Group. The rate of visual field change in the ocular hypertension treatment study. Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):224-7. doi: 10.1167/iovs.10-7117.
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    Brandt JD, Gordon MO, Gao F, Beiser JA, Miller JP, Kass MA; Ocular Hypertension Treatment Study Group. Adjusting intraocular pressure for central corneal thickness does not improve prediction models for primary open-angle glaucoma. Ophthalmology. 2012 Mar;119(3):437-42. doi: 10.1016/j.ophtha.2011.03.018. Epub 2011 Jun 25.
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    De Moraes CG, Demirel S, Gardiner SK, Liebmann JM, Cioffi GA, Ritch R, Gordon MO, Kass MA; Ocular Hypertension Treatment Study Group. Effect of treatment on the rate of visual field change in the ocular hypertension treatment study observation group. Invest Ophthalmol Vis Sci. 2012 Apr 2;53(4):1704-9. doi: 10.1167/iovs.11-8186.
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    Kymes SM, Lambert DL, Lee PP, Musch DC, Siegfried CJ, Kotak SV, Stwalley DL, Fain J, Johnson C, Gordon MO. The development of a decision analytic model of changes in mean deviation in people with glaucoma: the COA model. Ophthalmology. 2012 Jul;119(7):1367-74. doi: 10.1016/j.ophtha.2012.01.054. Epub 2012 Apr 25.
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    Mansberger SL, Gordon MO, Jampel H, Bhorade A, Brandt JD, Wilson B, Kass MA; Ocular Hypertension Treatment Study Group. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study. Ophthalmology. 2012 Sep;119(9):1826-31. doi: 10.1016/j.ophtha.2012.02.050. Epub 2012 May 16.
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    Gardiner SK, Demirel S, De Moraes CG, Liebmann JM, Cioffi GA, Ritch R, Gordon MO, Kass MA; Ocular Hypertension Treatment Study Group. Series length used during trend analysis affects sensitivity to changes in progression rate in the ocular hypertension treatment study. Invest Ophthalmol Vis Sci. 2013 Feb 15;54(2):1252-9. doi: 10.1167/iovs.12-10218.
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    Zangwill LM, Jain S, Dirkes K, He F, Medeiros FA, Trick GL, Brandt JD, Cioffi GA, Coleman AL, Liebmann JM, Piltz-Seymour JR, Gordon MO, Kass MA, Weinreb RN; Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study. The rate of structural change: the confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study. Am J Ophthalmol. 2013 Jun;155(6):971-82. doi: 10.1016/j.ajo.2013.01.020. Epub 2013 Mar 14.
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    23357622
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    Gardiner SK, Demirel S, Gordon MO, Kass MA; Ocular Hypertension Treatment Study Group. Seasonal changes in visual field sensitivity and intraocular pressure in the ocular hypertension treatment study. Ophthalmology. 2013 Apr;120(4):724-30. doi: 10.1016/j.ophtha.2012.09.056. Epub 2013 Jan 26.
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