Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00350428 |
| Other study ID # |
R221/13/2001 |
| Secondary ID |
SQGL05 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
July 7, 2006 |
| Last updated |
October 23, 2006 |
| Start date |
October 2001 |
| Est. completion date |
October 2007 |
Study information
| Verified date |
October 2004 |
| Source |
Singapore National Eye Centre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU) |
| Study type |
Interventional
|
Clinical Trial Summary
This is a randomised controlled clinical trial to compare laser peripheral iridotomy (LPI)
and primary phacoemulsification with intra-ocular lens implantation (phaco/IOL) in the
treatment of acute primary angle-closure glaucoma (APACG). Following successful medical
lowering of raised intra-ocular pressure (IOP) and control of intraocular inflammation,
patients presenting to Singapore National Eye Centre and Singapore General Hospital with
acute primary angle-closure glaucoma who meet the eligibility are randomised to one of the
two treatment arms: laser peripheral iridotomy and primary phacoemulsification with
intra-ocular lens implantation. These patients will be monitored closely for 2 years
post-operatively.
Description:
AIMS
The objective of this study is to conduct a randomised controlled clinical trial to compare
LPI and primary phacol/IOL in the treatment of APACG.
The specific aim is to compare long-term IOP control in patients who undergo LPI with
patients who undergo primary phaco/IOL. At the same time the following will be studied.
1. To evaluate the safety of these two techniques for the treatment of APACG
2. To assess the development of PAS
3. To establish if LPI and primary phaco/IOL are as effective in preventing the recurrence
of acute attack in eyes with APACG
TREATMENT PLAN
Initial Medical Treatment
Patients with APACG will be treated initially for the acute attack with medical treatment.
The initial treatment is standardized to the following:
1. Intravenous acetazolamide (Diamox) 500 mg stat
2. Oral acetazolamide 250 mg tid to qid with Span K 1.2 g om
3. Topical beta-blocker (Timolol 0.5%) bid or Brimonidine bid if beta-blockers are
contra-indicated.
4. Topical pilocarpine 4% qid
5. Topical steroids
6. Intravenous mannitol 20% at 1-2g/kg at 4 hours after initiation of treatment if IOP is
not reduced by 20% of initial IOP unless contra-indicated due to systemic disease eg.
Congestive heart failure.
7. A second infusion of intravenous mannitol 20% at 2g/kg at 12 hours after initiation of
treatment if IOP is still not reduced by 20% of initial IOP
Response to Initial Treatment and Evaluation of Cataract
Patients are divided into 2 categories based on IOP after 24 hours of initiation of medical
treatment: (a) APACG with IOP £ 30 mmHg (b) APACG with IOP > 30 mmHg.
Patients with IOP £ 30 mmHg are evaluated clinically for the presence of cataract and
further divided into those with cataract and those without cataract. Patients with cataract
are defined as those with best corrected visual acuity equal or less than 6/15 due to lens
opacity in the opinion of a consultant grade ophthalmologist.
Note: Eyes with intumescent cataract (phacomorphic glaucoma), subluxated lens or anterior
chamber depth differing by more than 0.3 mm are excluded.
Eligible patients with informed consent are randomised.
Laser Peripheral Iridotomy
1. In addition to the consultants, LPI may be performed by registrars, senior registrars
and fellows who have observed and been taught by the glaucoma consultants and are
deemed to be able to perform the procedure to a high standard.
2. LPI is performed when the cornea is sufficiently clear (usually within 72 hours)
following the lowering of the IOP medically.
3. Technique for LPI to be standardized to sequential argon-Nd-YAG Laser PI.
4. LPI should be sited at the superior nasal or superior temporal quadrant.
5. The size of opening should be ³ 200mm.
6. Following successful LPI, topical eyedrops are continued for one week after the
procedure. Oral Diamox is discontinued.
7. If the initial attempt is unsuccessful, LPI at a second alternative site will be
attempted. If the second attempt remains unsuccessful, patient will be considered as
failure .
Phacoemulsification with Intra-ocular Lens Implantation
1. All phacoemulsification with intraocular lens implantation are to be performed by
consultant surgeons. The panel of surgeons is formed from the group of co-investigators
of this study.
2. Phacoemulsification will be carried out between 5 to 7 days following the lowering of
the IOP. This is to allow for improved corneal clarity and reduction of intra-ocular
inflammation.
3. Gutt pilocarpine to be stopped on morning of operation.
4. Pre-operative intravenous mannitol 20% at 1-2g/kg is given 2 hours before the start of
operation for those subjects with an IOP persistently raised above 21mmHg.
5. Clear corneal incision.
6. Viscoelastic agent to be injected 360 degrees circumferentially in the angles to deepen
the anterior chamber. There will be no other angle augmentation procedure using
surgical instruments.
7. A standard foldable IOL (Type of IOL: Acrysof MA60)
8. Viscoelastic agent should be removed at the end of operation as far as possible.
9. Oral Diamox 250 mg to be given stat post-operatively to reduce post-operative IOP
spike.
10. Following successful phacoemulsification with IOL implantation, topical steroids and
antibiotics are given. Topical pilocarpine, timolol and oral Diamox are stopped.
IOP Lowering Medication
With regard to the determination of endpoints IOP evaluation will be considered from
post-operative week 3 onward. This is to allow for treatment of short-term surgery related
IOP fluctuation.
During the follow up period, if a rise of IOP occurs, i.e. IOP is between 22 to 24 mmHg on
two occasions within one month or IOP ³ 25 mmHg on one occasion, IOP lowering medication
will be started.
FOLLOW-UP
Post operation visit Window period
1st week ± 2 days 3rd week ± 5 days 6th week ± 7 days 3rd month ± 2 weeks 6th month to 2nd
year ± 3 weeks
At the completion of the trial patient will receive normal clinical follow up of 4-6 monthly
thereafter whilst the data will not be collected for this study.
The primary objective of the study is to compare IOP control between these two treatment
groups.
STATISTICAL CONSIDERATIONS
Sample Size Calculation:
The primary objective of the study is to compare long-term intra-ocular pressure (IOP)
control between the two groups.
The proportion of the subjects whose IOP are not successfully controlled in the LPI group
can be estimated as 60% (Aung T 2001). And the proportion of the subjects whose IOP are not
successfully controlled in the phacoemulsification with intra-ocular lens implant group is
about 20% under clinical estimation. Hence, the study needs a sample size of 70 patients
(Machin, Campbell, Fayers & Pinol, 1997), 35 in each group. This will be sufficient to
detect a 60% vs. 20% of proportion of the subjects who develop increasing IOP between two
groups with a two-sided test with a power 90% while the significance level is controlled at
5%.
Statistical Analysis Plan
All statistical analysis will be carried out on an intention-to-treat basis. In the event of
lost to follow-up, patients will still be included in the analysis for the duration that
they are observed, and the last IOP which is assessed before lost to follow-up will be used
for data analysis.
To compare long-term IOP control between two treatments, Pearson χ2 test or Fisher’s exact
test will be used. The evaluation of the incidence of recurrence of an acute attack in eyes
with APACG will be carried out using Fisher’s exact test. Logistic regression will be
carried out to adjust for relevant covariates.
The time interval for the subsequent increase in IOP to occur after LPI or phacol/IOL is to
be recorded. Kaplan-Meier life table analysis can be applied to assess the survival time
(failure being defined as any need for further glaucoma treatment) of two groups, and Log
rank test will be used to compare the two survival curves. In addition, The Cox regression
will be used to adjust for covariates where applicable.
An interim statistical analysis will be carried out after all patients have completed 6
months follow-up.
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