Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03875911 |
| Other study ID # |
17-000432 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
March 30, 2019 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
January 2024 |
| Source |
University of California, Los Angeles |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In this Pilot explorative study, the investigators are going to estimate and compare the
outcomes of three different delivery methods of MMC for Trabeculectomy: a subconjunctival
injection of MMC 0.002% at the site of future Trabeculectomy two to four weeks before the
surgery, a subconjunctival injection of MMC 0.01% intraoperatively and topical sponge applied
MMC 0.02% intraoperatively (typical use) in patients with Primary Open Angle Glaucoma who did
not have any filtering surgeries before.
After obtaining informed consent from the patients, the patients are randomly divided into
three groups via a block randomization method: Group A receives 0.1 mL MMC 0.002 % (0.1mL MMC
0.02mg/mL) subconjunctival injection preoperatively in superior conjunctiva at the site of
future Trabeculectomy surgery. Group B receives 0.1mL MMC 0.01% subconjunctival injection
intraoperatively at the site of Trabeculectomy and Group C receives conventional sponge
delivery of MMC 0.02% intraoperatively. To avoid observer bias during postoperative
evaluation of results, IOP staff obtaining measurements of IOP will be masked to the
randomization allocation.
All groups undergo conventional Trabeculectomy surgery (fornix-based) as scheduled, and the
same routine follow up and post-op regimen will be scheduled for all three groups. Patients
are routinely visited in the clinic at first day postoperatively, one week (+/-2 days), one
month (+/-1 week), three months (+/-2 weeks), six months (+/-3 weeks) and finally at one year
(+/-(4 weeks)). In each of these visits we will be assessing: Visual acuity, intraocular
pressure, number and type of glaucoma medication, slit lamp examination of the anterior
segment and fundus examination.
Description:
Purpose:
To obtain estimates of the effect on intraocular pressure and side effects of three delivery
methods of Mitomycin C (MMC) compared among each other: preoperative subconjunctival
injection of 0.1 mL MMC 0.002%, subconjunctival injection of 0.1 mL MMC 0.01%
intraoperatively, and conventional sponge applied MMC (0.02%) during trabeculectomy surgery
in patients with Primary Open Angle Glaucoma who did not have any filtering surgeries before.
Objective:
To obtain estimates for intraocular pressure reduction among three delivery methods of MMC
compared among each other: preoperative subconjunctival injection, intraoperative
subconjunctival injection, and intraoperative topical use during trabeculectomy surgery, and
to report any associated adverse effects.
Null hypothesis:
There is no use of hypothesis testing in this pilot study.
Alternative hypothesis:
There is no use of hypothesis testing in this pilot study.
The effect and safety of MMC subconjunctival injection either preoperatively or
intraoperatively has been previously investigated in Pterygium surgery (Khakshoor H, Razavi
ME, Daneshvar R, Shakeri MT, Ghate MF, Ghooshkhanehi H. Am J Ophthalmol. 2010
Aug;150(2):193-8. Preoperative subpterygeal injection vs intraoperative mitomycin C for
pterygium removal: comparison of results and complications).
Previous studies comparing effectiveness of subconjunctival injection of MMC vs
sponge-applied MMC have shown inconsistent results. In one retrospective study, Mitomycin-C
applied by injection resulted in significantly lower IOP, and the need for fewer glaucoma
medications, however description of methods is incomplete. (Lim MC. A comparison of
trabeculectomy surgery outcomes with mitomycin-C applied by intra-Tenon injection versus
sponge method. American Glaucoma Society 23rd Annual Meeting; 2013, San Francisco, CA). One
retrospective study showed similar efficacy and safety of intraoperative MMC injection
compare to sponge application in trabeculectomy surgery with overall lower IOP in the
injection group and main advantages being a large surface area of exposure and a predictable
dose of deliver when the injection was performed. No difference in postoperative
complications between groups was observed. A small sample size (30) in each group might
prevent finding statistical significant results. (Khouri AS, Huang G, Huang LY.
Intraoperative Injection vs Sponge-applied Mitomycin C during Trabeculectomy: One-year Study.
J Curr Glaucoma Pract 2017;11(3):101-106). A previous case report on preoperative
administration of MMC for Trabeculectomy showed reduction of IOP with short follow-up (6
months) Hung PT, Lin LL, Hsieh JW, Wang TH. Preoperative mitomycin-C subconjunctival
injection and glaucoma filtering surgery. J Ocul Pharmacol Ther. 1995;11(3):233-241.
One RCT with a follow-up of 3 years compared outcomes of intraoperative injection versus
sponge-applied MMC and no significant difference in IOP was found however a more favorable
bleb morphology was found in the injection group which is correlated with better function and
long-term success of Trabeculectomy ( Esfandiari, Hamed et al. Treatment Outcomes of
Mitomycin C-Augmented Trabeculectomy, Sub-Tenon Injection versus Soaked Sponges, after 3
Years of Follow-up Ophthalmology Glaucoma , Volume 1 , Issue 1 , 66 - 74)
In this study the comparison will be the timing and route of delivery of MMC in all three
groups, having found inconsistent reports in the literature and very scarce data on the
effect of preoperative subconjunctival MMC the investigators would like to further explore in
this pilot study the effect of subconjunctival injection on IOP reduction for trabeculectomy
at preoperative and intraoperative phases. Since there is no group receiving placebo, the
inclusion of a sham injection will not affect the outcomes compared to GROUP C and could
increase preoperative risks to patients. The same methodology has been applied in two
previous randomized controlled trials. (Pakravan M, Esfandiari H, Yazdani S, et al. Mitomycin
C-augmented trabeculectomy: subtenon injection versus soaked sponges: a randomized clinical
trial Br J Ophthalmol 2017;101:1275-1280 and Khan F, Niazi S, Awais M et all. Effectiveness
of Preoperative Subconjunctival Injection of Mitomycin-C in Primary Pterygium Surgery Journal
of the College of Physicians and Surgeons Pakistan 2017, Vol. 27 (2): 88-91)
Glaucoma patients who need glaucoma surgery, such as trabeculectomy, have ongoing damages
that cannot be managed only with medication such as drops, and pressure reduction is
absolutely crucial in preserving visual function in these patients, hence any possible action
that can add to this reduction is valuable.
On the other hand, there are several risks associated with the topical applied MMC usage at
the time of surgery mainly due to the inability to precisely quantify the amount of MMC
delivered by the sponge application which was shown to be far less with the injection of MMC
by delivering a predicted volume either at surgery or before the surgery which are mentioned
in the first two paper references.
The selected concentrations for the MMC injection are based on pharmacological studies
performed on ocular tissue in which the concentration achieved after subconjunctival
injection was established.
STUDY DESIGN This is a multicenter, randomized, controlled pilot study with a main objective
of obtaining estimates of differences in IOP reduction among three methods of delivery of
mitomycin C for use in trabeculectomy surgery.
The injectors and patients are unmasked in this study while the evaluators are masked.
This study will be performed at the Glaucoma Division of Stein Eye Institute-UCLA Los
Angeles, CA.
METHODS
Patients who met inclusion criteria and had signed an informed consent will then be
randomized into three groups as follows:
- Group A: Patients will receive a subconjunctival injection of 0.1mL MMC 0.02mg/mL which
corresponds to 0.002% (a tenth of the concentration of conventional topical MMC use) at
the site of future trabeculectomy surgery two to four weeks in advance. A follow-up
phone call 1 week after the MMC injection will assess any side effects of the procedure.
If side effects are reported by the patient an appointment will be schedule for a follow
up in-office visit and appropriate treatment will be delivered. On the day of
conventional trabeculectomy no MMC will be injected. Follow-up will be scheduled for one
year.
- Group B: On the day of conventional trabeculectomy patients will receive a
subconjunctival injection intraoperatively of 0.1 mL MMC 0.1mg/mL which corresponds to
0.01% (half the concentration of conventional topical MMC use) at the site of
trabeculectomy. Surgeon will irrigate the surface of the eye after MMC injection to
remove any MMC that might have leaked out. Follow-up will be scheduled for one year.
- Group C: On the day of conventional trabeculectomy patients will receive MMC by applying
a sponge soaked in 1mL of MMC 0.2 mg/mL (0.02%) for 1 minute to the site of
trabeculectomy surgery followed by irrigation. MMC is standard of care for
trabeculectomy surgery at UCLA. This differs from the proposed research because the MMC
will be administered as an injection either two to four weeks before the surgery in
Group A or intraoperatively in Group B rather than the usual topical administration on
the day of surgery (Group C). Follow-up will be scheduled for one year.
The concentration of MMC in each group were chosen according to the delivery method and the
timing of exposition of the tissue to the MMC in order to prevent complications from
overdose. Based on experimental studies on ocular tissues that evaluated the final amount of
MMC delivered to scleral tissue and finding a similar result when using subconjunctival
injection of 0.02% with immediate irrigation and 0.002% without irrigation, the investigators
chose the latter for group A. Few studies evaluated MMC subconjunctival injection one month
before pterygium surgery using 0.02% and 0.015% with a follow-up of 3 years establishing
safety of this approach. For group B the investigators chose a similar methodology of a
previous RCT comparing subconjunctival injection versus topical administration of MMC for
trabeculectomy that used a reduced concentration of 0.01%.
Data collection will be as follows: At preoperative visit, postoperative day one, one week
(+/- 2 days), one month (+/- 1 week), three months (+/- 2 weeks), six months (+/- 3 weeks)
and one year (+/- 4 weeks). The data will be recorded in the REDCap (Research Electronic Data
Capture) software which has free access and allows for easy recording and uploading of
imaging (VF, Optic nerve OCT, AS-OCT and bleb photography) for future analysis.
In each of these visits, the following data will be collected: Visual acuity, intraocular
pressure, number and type of glaucoma medication, slit lamp examination of the anterior
segment, fundus examination and adverse events if present. Visual field and optic nerve OCT
will also be included in the preoperative evaluation and at 12 months postoperatively.
For better assessment of the bleb morphology, the investigators will include a clinical grade
system, slit lamp photography, and AS-OCT [Anterior segment module of Spectralis OCT device
(Heidelberg Engineering, Inc., Heidelberg, Germany)] of the bleb.
For the clinical description of the bleb and a more standardized comparison of the
morphological changes over time, the investigators included at every postoperative visit the
description of the bleb using the Moorfields Bleb Grading System (MBGS) which captures more
morphological features and regional vascularity compared to other systems. (Wells AP, Ashraff
N, HalL RC et all Comparison of Two Clinical Bleb Grading Systems Ophthalmology
2006;113:77-83).
The bleb photography will be included at the Month 3 and Month 12 postoperative visits and
AS-OCT at 1,3,6 and 12 Month follow-ups. The inclusion of AS-OCT allows for evaluation of the
internal structure of the bleb that has been shown to have prognostic implications for
outcomes of surgery. Kokubun T, Tsuda S, Kunikata H et all. Anterior-Segment Optical
Coherence Tomography for Predicting Postoperative Outcomes After Trabeculectomy, Current Eye
Research, DOI: 10.1080/02713683.2018.1446535
Block randomization:
To ensure the balance of sample size between three treatment groups, block randomization is
used for treatment assignment. Specifically, each block consists of 6 patients, including 2
patients in each of three treatment groups, and all possible permutations of a sequence of
treatment assignment for these 6 patients are generated, such as AABBCC, ABCABC, etc. A
random number is then generated to select a block of treatment assignment for 6 patients
among all possible blocks, and a sequence of such random blocks will form the sequence of
treatment assignment for all patients after their enrollment.
