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

Sponsor

University of Parma (Other)

Overall Status

Completed

CT.gov ID

NCT01655758

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Jan 1, 2002

Actual Primary Completion Date :

Dec 1, 2003

Actual Study Completion Date :

Feb 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: timolol 60-day treatment phase with 0.5% timolol eyedrops, b.i.d.	Drug: 0.5% timolol Other Names: 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 Names: cosopt (MSD)
Active Comparator: xalatan 60-day treatment phase with 0.005% latanoprost, eyedrops, QD	Drug: Latanoprost Other Names: xalatan (pfizer)
Active Comparator: travatan 60-day treatment phase with 0.004% travoprost, eyedrops, QD	Drug: Travoprost Other Names: travatan (Alcon)
Active Comparator: lumigan 60-day treatment phase with 0.03% bimatoprost, eyedrops, QD	Drug: Bimatoprost Other Names: lumigan (Allergan)

Outcome Measures

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 [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

visual field [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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,