24-hour Control of Intraocular Pressure (IOP) in Ocular Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01655758
Recruitment Status : Completed
First Posted : August 2, 2012
Last Update Posted : August 2, 2012
Information provided by (Responsible Party):
Stefano Gandolfi, University of Parma

Brief Summary:
This study was designed to compare the 24-hour efficacy on intra ocular pressure (IOP) of drugs acting either on aqueous humor production ("inflow drugs") or on aqueous humor outflow ("outflow drugs") in human eyes affected by ocular hypertension and virgin to treatment. The enrolled patients will be exposed, in a cross-over design, to n = 2 aqueous suppressants and n= 3 uveoscleral outflow enhancers, and 24 hr IOP will be measured. It is hypothesised that outflow drugs may offer a better and more stable control of IOP through the 24 hours.

Condition or disease Intervention/treatment Phase
Ocular Hypertension Drug: 0.5% timolol Drug: timolol-dorzolamide fixed combination Drug: Latanoprost Drug: Travoprost Drug: Bimatoprost Phase 4

Detailed Description:
(a) study design: Prospective, open label, investigator-masked clinical trial, with cross-over design, both eyes treated, OD chosen for analysis; (b) study population: patients, showing ocular hypertension, who were never exposed to hypotensive treatment (see inclusion and exclusion criteria for details). (c) study drugs: Timolol and dorzolamide will be chosen as inflow drugs. The three prostaglandin analogues (PGA) Latanoprost, travoprost and bimatoprost will be chosen as outflow drugs. (d) study flow-chart: upon enrollment, patients will be initiated to the following schedule: 60 days timolol 0.5% bid, 60 days washout, 60 days timolol 0.5%-dorzolamide 2% fixed combination bid, 60 days washout, 60 days PGA1, 60 days washout, 60 days PGA2, 60 days washout, 60 days PGA3. Patients were assigned to the PGAs according to a sequence (L-T-B) randomly generated. Data will be collected at baseline and at the and of each study phase (i.e. active treatment and washout)(e) main efficacy outcome: change in the mean IOP (with respect to baseline) at the end of each study phase and change of IOP (with respect to baseline) at the different time points of the 24-hour phasing. IOP will be measured at 8 a.m., 11 a.m., 3 p.m., 6 p.m. and 9 p.m. by means of Goldmann applanation tonometry at the slit lamp. At midnight, 2 a.m. and 6 a.m. the Tonopen in supine position will be used. (f) statistics: the analysis of co-variance (ANCOVA) for paired samples with Bonferroni correction will be adopted. A minimum sample size of 51 patients is needed for a minimal expected difference in mean IOP between inflow and outflow drugs = 2.5 mmHg, with an estimated pooled variance = 4 , a power = 90% and an alpha probability = 5%.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The 24 Control of IOP in Ocular Hypertension: a Cross-over Study on Inflow Versus Outflow Drugs.
Study Start Date : January 2002
Actual Primary Completion Date : December 2003
Actual Study Completion Date : February 2004

Arm Intervention/treatment
Active Comparator: timolol
60-day treatment phase with 0.5% timolol eyedrops, b.i.d.
Drug: 0.5% timolol
Other Name: timoptol (MSD)
Active Comparator: 'timolol-dorzolamide fixed combination'
60-day treatment phase with the fixed combination of 0.5% timolol-2% dorzolamide, eyedrops, b.i.d.
Drug: timolol-dorzolamide fixed combination
Other Name: cosopt (MSD)
Active Comparator: xalatan
60-day treatment phase with 0.005% latanoprost, eyedrops, QD
Drug: Latanoprost
Other Name: xalatan (pfizer)
Active Comparator: travatan
60-day treatment phase with 0.004% travoprost, eyedrops, QD
Drug: Travoprost
Other Name: travatan (Alcon)
Active Comparator: lumigan
60-day treatment phase with 0.03% bimatoprost, eyedrops, QD
Drug: Bimatoprost
Other Name: lumigan (Allergan)

Primary Outcome Measures :
  1. change in the mean IOP at the end of each phase vs baseline, and change of IOP at the different time points of the 24-hour phasing with respect to baseline [ Time Frame: IOP will be measured, at baseline, on day 60, 120, 180, 240, 300, 360,420,480 and 540, at 8 a.m., 11 a.m., 3 p.m., 6 p.m., 9 p.m., midnight, 2 a.m. and 6 a.m. ]

    Goldmann Applanation tonometry (GAT): 2 readings averaged. If >2 mmHg difference between the two, a further reading will be performed. GAT will be adopted during the day, and performed at the slit lamp in sitting position.

    Tonopen: 4 readings averaged. Tonopen will be used during the night, and the measurements will be perfomred on patients laying in bed in supine position.

Secondary Outcome Measures :
  1. visual field [ Time Frame: visual field (24/2 SITA) will be performed at screening and at the end of the study (i.e. upon completion of the last cross-over arm, 540 days after baseline) ]
    Humphrey Field Analyzer, 24/2 SITA standard

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • IOP > 22 mmHg and < 30 mmHg on at least three readings on separate days ,
  • Open angle on gonioscopy,
  • CCT > 550 m,
  • optic disk classified as "within normal limits" by Moorfields Regression analysis, HRTII,
  • normal visual field (standard achromatic perimetry, Humphrey Field Analyzer, 24/2 SITA standard),
  • Age > 40 and < 70 years,
  • refraction between - 5 and + 2 dyopters,
  • best corrected visual acuity better than 0.2 LogMAR,

Exclusion Criteria:

  • PEX
  • PDS
  • ocular comorbidiities other than refractive problems and/or mild dry eye
  • history of diabetes
  • treatment with systemic beta blockers and steroids
  • previous treatment with ocular hypotensive drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01655758

University Eye Clinic
Parma, Italy, 43100
Sponsors and Collaborators
University of Parma
Principal Investigator: STEFANO GANDOLFI, MD University of Parma

Responsible Party: Stefano Gandolfi, professor of ophthalmology and chairman,, University of Parma Identifier: NCT01655758     History of Changes
Other Study ID Numbers: UParma2004crossover
First Posted: August 2, 2012    Key Record Dates
Last Update Posted: August 2, 2012
Last Verified: July 2012

Keywords provided by Stefano Gandolfi, University of Parma:
24-hour IOP
outflow drugs
inflow drugs

Additional relevant MeSH terms:
Ocular Hypertension
Vascular Diseases
Cardiovascular Diseases
Eye Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors