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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Stefano Gandolfi, University of Parma
ClinicalTrials.gov Identifier:
NCT01655758
First received: July 21, 2012
Last updated: August 1, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Ocular Hypertension
Drug: 0.5% timolol
Drug: timolol-dorzolamide fixed combination
Drug: Latanoprost
Drug: Travoprost
Drug: Bimatoprost
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (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.

Resource links provided by NLM:


Further study details as provided by University of Parma:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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:
  • 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) ] [ Designated as safety issue: Yes ]
    Humphrey Field Analyzer, 24/2 SITA standard


Enrollment: 61
Study Start Date: January 2002
Study Completion Date: February 2004
Primary Completion Date: December 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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%.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655758

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

No publications provided

Responsible Party: Stefano Gandolfi, professor of ophthalmology and chairman,, University of Parma
ClinicalTrials.gov Identifier: NCT01655758     History of Changes
Other Study ID Numbers: UParma2004crossover
Study First Received: July 21, 2012
Last Updated: August 1, 2012
Health Authority: Italy: Ministry of Health

Keywords provided by University of Parma:
glaucoma
24-hour IOP
outflow drugs
inflow drugs

Additional relevant MeSH terms:
Hypertension
Ocular Hypertension
Vascular Diseases
Cardiovascular Diseases
Eye Diseases
Timolol
Latanoprost
Bimatoprost
Travoprost
Dorzolamide
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014