Study of Antibiotic Prophylaxis for Endophthalmitis Following Cataract Surgery

Sponsor

City, University of London (Other)

Overall Status

Completed

CT.gov ID

NCT00136344

Collaborator

The European Society of Cataract and Refractive Surgeons(ESCRS) (Other), Santen Gmbh (Other)

35,000

Enrollment

Locations

Duration (Months)

1458.3

Patients Per Site

45.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cataract is the most important cause of visual impairment and decreased mobility in the elderly. While surgery is usually successful, it is also responsible for permanent loss of vision in up to 0.1% of patients due to severe post-operative infection (endophthalmitis). Because of this risk, surgery is typically performed on one eye at a time leaving the patient with a monocular cataract causing considerable visual impairment with reduction in mobility and quality of life. A second operation is required which often takes place up to one year later.

It is not known at present whether the post-operative complication of endophthalmitis can be prevented by perioperative use of antibiotics. This randomised study (masked and placebo-controlled for topical levofloxacin and unmasked for intracameral injection of cefuroxime) sets out to test in 4 groups, each of 8,750 cataract surgery patients, if either topical antibiotic (levofloxacin) perioperatively or an intraocular (intracameral) injection of antibiotic (cefuroxime) at the end of phacoemulsification cataract surgery or the combination provides effective prophylaxis of post-operative infection (endophthalmitis) compared to controls in whom perioperative antibiotics are not used. The result will provide a scientific basis for prophylaxis of infection (endophthalmitis) following cataract surgery in Europe as well as an accurate figure for the incidence of endophthalmitis following phacoemulsification cataract surgery in Europe for the first time.

Condition or Disease	Intervention/Treatment	Phase
Endophthalmitis	Drug: Cefuroxime Drug: Levofloxacin	N/A

Detailed Description

Cataract extraction with intra-ocular lens implantation is the most commonly performed surgical procedure in the elderly population in Europe. The frequency varies in different European Union (EU) countries involving 2 to 7 per 1000 population per annum. A population with an ever-increasing proportion of the elderly is advancing this figure with numbers requiring surgery expected to increase by 70% by 2006. While technical advances (phacoemulsification) have enhanced the efficacy of the procedure, the possibility of serious post-operative infection with loss of vision remains the most important unsolved problem.

In the absence of scientific evidence, the European Society of Cataract and Refractive Surgeons (ESCRS) wishes to determine whether one currently developed method of delivering antibiotics intraocularly in Sweden is of benefit compared to surgery without the use of perioperative antibiotics, as currently practised in many European centres, or to the use of frequent application of topical antibiotic drops perioperatively. The ESCRS also wishes to assess possible risk factors for later endophthalmitis.

This study requires four groups of 8,750 patients - 35,000 in all - to demonstrate reductions of currently reported rates of endophthalmitis (approximately 0.3%) in patients where no intraocular antibiotics are used, or where they are used by the subconjunctival route. Other studies using intraocular vancomycin have reported results as low as 0.05%, but these studies were not standardised or controlled and the results were anecdotal. In addition, vancomycin should not be used for routine prophylaxis and should only be used as the antibiotic of 'last resort'.

This multi-centre randomised study involves 24 operating units in 8 EU countries (Austria, Belgium, England, Germany, Italy, Poland, Portugal and Spain) and Turkey. Results in 8,750 patients receiving an intracameral injection of antibiotic (cefuroxime) at the end of surgery will be compared to 8,750 patients receiving topical antibiotic (levofloxacin) prophylaxis before and at the end of surgery, 8,750 patients receiving the combination and 8,750 patients receiving neither regime; in addition, all patients will receive povidone iodine antiseptic prophylaxis prior to surgery and post-operative levofloxacin from days 1 to 6 to prevent wound infection.

This group size will be sufficiently large to ensure at least 80% statistical power to detect a reduction of incidence from 0.25% to 0.08% using 5% significance level tests.

Surgical data from all patients will be collected directly into computers based within each operating theatre and transmitted to a central server in Glasgow (University of Strathclyde). Follow-up data for the presence or absence of endophthalmitis will be collected from all patients at post-operative visits and similarly recorded on computers for transmission to the central server. Sophisticated techniques will be used to check all data as it is uploaded.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double

Primary Purpose:

Prevention

Official Title:

Antibiotic Prophylaxis for Cataract Surgery Version 7e January 22 2003

Study Start Date :

Sep 1, 2003

Study Completion Date :

May 1, 2006

Outcome Measures

Primary Outcome Measures

Prevention of post-operative endophthalmitis following phacoemulsification cataract surgery in Europe due to use of perioperative antibiotics []
Incidence of endophthalmitis in Europe following phacoemulsification cataract surgery []

Secondary Outcome Measures

Effect of risk factors on the presentation of endophthalmitis in Europe following phacoemulsification cataract surgery []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All patients, including diabetics, undergoing routine cataract surgery in each unit taking part in the study

Exclusion Criteria:

Patients who do not wish to take part in the trial
Patients allergic to penicillins and cephalosporins.
Long-term nursing home patients
Patients with only one eye
Pregnancy.
Children less than 18 years old.
All severely 'at-risk' groups for infection including:
Severe atopic keratoconjunctivitis;
Severe active blepharitis;
Ocular cicatricial pemphigoid.
Patients with complicated cataracts such as traumatic or subluxated
Patients having combined operations with cataract surgery such as trabeculectomy or a corneal graft.
Patients known to be allergic to povidone iodine (very rare) or any other known hypersensitivity to any components of the study medications.
Patients who are incapacitated mentally and incapable of giving consent.
Patients with severe thyroid disease
Open infection anywhere, infection of lacrimal drainage channels or infection around the eye

Contacts and Locations

Locations

	Site	City	Country
1	University Eye Clinic, Paracelsus Private Medical University	Salzburg	Austria
2	University Hospital Antwerp, UZA Ophthalmology	Antwerp	Belgium
3	University of Gent, Universitaire Zeikenhuis	Gent	Belgium
4	Jan Yperman Ziekenhuis	Ieper	Belgium
5	Centre Hospitalier Universitaire	Liege	Belgium
6	Oogheelkunde	Melveren	Belgium
7	Augenklinik Ahaus	Ahaus	Germany
8	Azienda Ospedaliera di Desenzano del Garda	Desenzano	Italy
9	Ospedale Borgo Trento	Verona	Italy
10	Kierownik Katedry i Kliniki	Warsaw	Poland
11	University Hospital	Coimbra	Portugal
12	Instituto Oftalmologico VISSUM	Alicante	Spain
13	La Candelaria University Hospital	La Candelaria, Tenerife	Spain
14	Hospital Universitario de Canarias	La Laguna, Tenerife	Spain
15	Hospital Oftalmologico Internacional	Madrid	Spain
16	Dokuz Eylul University	Izmir	Turkey
17	Axminster Hospital	Axminster	United Kingdom
18	West of England Eye Unit, Royal Devon & Exeter Hospital (Wonford)	Exeter	United Kingdom
19	Ipswich Hospital	Ipswich	United Kingdom
20	Moorfields Eye Outreach Unit, Northwick Park Hospital	London	United Kingdom
21	Moorfields Eye Outreach Unit, St. George's Hospital	London	United Kingdom
22	St. Thomas' Hospital	London	United Kingdom
23	Oxford Eye Hospital	Oxford	United Kingdom
24	Sunderland Eye Infirmary	Sunderland	United Kingdom