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 0.5% 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 peri-operative use of antibiotics. This randomised study (masked and placebo-controlled for topical levofloxacin and unmasked for intra-cameral injection of cefuroxime) sets out to test in 4 groups, each of 8,750 cataract surgery patients, if either topical antibiotic (levofloxacin) peri-operatively or an intra-ocular (intra-cameral) 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 peri-operative 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	Intervention
Endophthalmitis	Drug: Cefuroxime  Drug: Levofloxacin

Further Study Details: 

Primary Outcomes: Prevention of post-operative endophthalmitis following phacoemulsification cataract surgery in Europe due to use of peri-operative antibiotics; Incidence of endophthalmitis in Europe following phacoemulsification cataract surgery
Secondary Outcomes: Effect of risk factors on the presentation of endophthalmitis in Europe following phacoemulsification cataract surgery
Expected Total Enrollment:  35000

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 EU countries involving 2 to 7 per 1000 population per annuum. 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 ESCRS wishes to determine whether one currently developed method of delivering antibiotics intra-ocularly in Sweden is of benefit compared to surgery without the use of peri-operative antibiotics, as currently practised in many European centres, or to the use of frequent application of topical antibiotic drops peri-operatively. 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 intra-ocular antibiotics are used, or where they are used by the sub-conjunctival route. Other studies using intra-ocular 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 (refer to page 13).

This multi-centre randomised study involves 24 operating units in 8 EU countries (Austria, Belgium, Denmark, England, France, Germany, Italy, Portugal and Spain) and Turkey. Results in 8,750 patients receiving an intra-cameral 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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, and as given below,

• 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00136344

David V Seal, MD      +44-20-7359-1475  Ext. -    dvseal@yahoo.co.uk
Fiona Lees, MSc      +44-141-548-3806  Ext. -    Fiona.Lees@cis.strath.ac.uk

United Kingdom, UK
      David Seal, London,  UK,  n1 8AQ,  United Kingdom; Recruiting

Study chairs or principal investigators

Peter Barry, FRCS,  Study Chair,  ESCRS (European Society of Cataract and Refractive Surgeons)   
Mary D''''Ardis,  Principal Investigator,  ESCRS   

Study ID Numbers:  MREC Ref. no. 02/5/46
Last Updated:  August 26, 2005
Record first received:  August 26, 2005
ClinicalTrials.gov Identifier:  NCT00136344
Health Authority: United Kingdom: National Health Service
ClinicalTrials.gov processed this record on 2005-08-30