Povidone-iodine Antisepsis for Strabismus Surgery

NCT ID: NCT00461656

Last Updated: 2013-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2012-12-31

Brief Summary

The purpose of this study is to compare the efficacy of 5 % vs. 1.25 % povidone-iodine (PI) as preoperative antiseptic prior to strabismus surgery in children as a prophylaxis of endophthalmitis. Given the low rate of endophthalmitis the conjunctival bacterial flora rate is used as surrogate marker to determine the effectiveness of topical PI in reducing or eliminating bacteria from the ocular surface at the time of the surgery. Secondary objective is a reduction of the incidence of postoperative endophthalmitis after strabismus surgery in young children.

Detailed Description

Background: Endophthalmitis after strabismus surgery in young children leads to blindness and loss of the affected eye. It is caused by conjunctival bacteria. PI solutions between 1% and 5% reduce the number of bacteria on the conjunctiva. The concentration used varies widely among clinics, from 1% to 5%. In vitro studies have shown that PI is paradoxically more effective at lower concentration, but in cataract surgery in elderly, 1% PI has been shown to be less effective than 5% PI. Dilution by tear fluid or binding of PI to proteins in tear fluid may lower its effectiveness. Since endophthalmitis after strabismus surgery especially affects young children and the bacterial flora of the conjunctiva in children is different from that in adults, the cataract PI study should be repeated in young children operated for strabismus.

Objective: To compare the efficacy of 5 % vs. 1.25 % povidone-iodine (PI) as preoperative antiseptic prior to strabismus surgery in children as a prophylaxis of endophthalmitis. Given the low rate of endophthalmitis the conjunctival bacterial flora rate is used as surrogate marker to determine the effectiveness of topical PI in reducing or eliminating bacteria from the ocular surface at the time of the surgery.

Design: The study is a multi-centre, prospective, randomized-controlled, parallel-groups, assessor-blind (microbiological assessments), investigator-initiated trial.

Study population: All children under 6 years of age attending the 15 participating clinics for routine strabismus surgery will be eligible for the study at the point that a strabismus operation is planned. The clinics (5 Dutch, 10 German) will each recruit approximately 20 patients. The minimum sample size is 2 x 100 patients.

Intervention: Diluted PI, 1.25% or 5%, will be prepared in a sterile fashion, and distributed in single-use dispensers. These will be coded for randomization. Before initiation of surgery, children randomized to the 5% PI group will have their conjunctival fornices irrigated with 5 ml PI 5%. Children randomized to the 1.25% PI group will have their conjunctival fornices irrigated with 5 ml PI 1.25%. Conjunctiva cultures for aerobic and anaerobic bacteria will be obtained (1) after general anesthesia has been established, (2) 5-10 min after PI irrigation, (3) after reattachment of the eye muscles and (4) after closing the conjunctiva with sutures.

Primary outcome: The difference in the mean numbers of bacterial colony forming units (CFUs) from pre-irrigation (l) to post-irrigation with PI (2-4).

Secondary outcome: Iodine excretion after surgery, assessed as urine iodine concentration per creatinine clearance.

Postoperative erosion of the cornea and corneal oedema. Both of these have been described as side-effects of PI use.

Nature and extent of the burden and risks associated with participation:

Risks are limited to the act of taking the four bacterial cultures, as both 1.25% PI and 5% PI are approved preoperative antiseptic applications of PI and both are used, rather indiscriminately, by the university departments of ophthalmology participating in the study.

Conditions

Strabismus; Surgery; Endophthalmitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Interventions

Preoperative conjunctival irrigation with 5% or 1.25% PI

Before initiation of surgery, children will have their conjunctival fornices irrigated with 5 ml PI 5% or with 5 ml PI 1.25%

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Children attending for routine strabismus surgery are eligible for the study. Criteria for inclusion:

1. Children < 6 years of age

2. undergoing surgery for strabismus for the first time, including any recession and/or resection surgery of the medial and/or lateral rectus muscles.

3. willing to take part in all aspects of the study with written informed consent on the study participation of the child provided by the parents.

Exclusion Criteria

1. Any history or current condition of hypersensitivity to iodine

2. Children on topical antibiotic within the last 30 days

3. Children with signs of acute conjunctivitis, blepharitis, dacryocystitis or respiratory infection within the last 30 days

4. Children with asthma or similar chronic, obstructive pulmonary disorder

5. Insufficiently treated amblyopia, i.e. a difference between the visual acuities of both eyes larger than 1 LogMARline.

6. Neurological or psychiatric disorder, medication, other eye disorder, decreased visual acuity caused by brain damage or trauma.

• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: collaborator

University Medicine Greifswald

OTHER

Sponsor Role: collaborator

Free University Medical Center

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Rotterdam Eye Hospital

UNKNOWN

Sponsor Role: collaborator

Laurentius Hospital Roermond

UNKNOWN

Sponsor Role: collaborator

Martin-Luther-Universität Halle-Wittenberg

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Erasmus Medical Center Rotterdam

Principal Investigators

Huibert J Simonsz, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Herminia Miño de Kaspar, PhD

Role: PRINCIPAL_INVESTIGATOR

Universitäts-Augenklinik Ludwig-Maximilian University Munich Germany

Locations

Ernst Moritz Arndt University

Greifswald, , Germany

Universitäts-Augenklinik

Magdeburg, , Germany

Universitäts-Augenklinik Ludwig-Maximilian University

Munich, , Germany

Dept. Ophthalmology Free University Medical Center

Amsterdam, , Netherlands

Dept. Ophthalmology Academical Medical Center

Amsterdam, , Netherlands

Dept. Ophthalmology

Leiden, , Netherlands

Dept. of Ophthalmology St. Laurentius Ziekenhuis

Roermond, , Netherlands

Rotterdam Eye Hospital

Rotterdam, , Netherlands

Dept. of Ophthalmology Erasmus Medical Center

Rotterdam, , Netherlands

Countries

Germany; Netherlands

References

Anderson RL, Vess RW, Carr JH, Bond WW, Panlilio AL, Favero MS. Investigations of intrinsic Pseudomonas cepacia contamination in commercially manufactured povidone-iodine. Infect Control Hosp Epidemiol. 1991 May;12(5):297-302. doi: 10.1086/646342.

Reference Type: BACKGROUND

PMID: 1865100 (View on PubMed)

Apt L, Isenberg S, Yoshimori R, Paez JH. Chemical preparation of the eye in ophthalmic surgery. III. Effect of povidone-iodine on the conjunctiva. Arch Ophthalmol. 1984 May;102(5):728-9. doi: 10.1001/archopht.1984.01040030584025.

Reference Type: BACKGROUND

PMID: 6721765 (View on PubMed)

Bannerman TL, Rhoden DL, McAllister SK, Miller JM, Wilson LA. The source of coagulase-negative staphylococci in the Endophthalmitis Vitrectomy Study. A comparison of eyelid and intraocular isolates using pulsed-field gel electrophoresis. Arch Ophthalmol. 1997 Mar;115(3):357-61. doi: 10.1001/archopht.1997.01100150359008.

Reference Type: BACKGROUND

PMID: 9076208 (View on PubMed)

Berkelman RL, Holland BW, Anderson RL. Increased bactericidal activity of dilute preparations of povidone-iodine solutions. J Clin Microbiol. 1982 Apr;15(4):635-9. doi: 10.1128/jcm.15.4.635-639.1982.

Reference Type: BACKGROUND

PMID: 7040461 (View on PubMed)

Binder CA, Mino de Kaspar H, Klauss V, Kampik A. [Preoperative infection prophylaxis with 1% polyvidon-iodine solution based on the example of conjunctival staphylococci]. Ophthalmologe. 1999 Oct;96(10):663-7. doi: 10.1007/s003470050471. German.

Reference Type: BACKGROUND

PMID: 10552160 (View on PubMed)

Caldwell DR, Kastl PR, Cook J, Simon J. Povidone-iodine: its efficacy as a preoperative conjunctival and periocular preparation. Ann Ophthalmol. 1984 Jun;16(6):577, 580.

Reference Type: BACKGROUND

PMID: 6611102 (View on PubMed)

Carothers TS, Coats DK, McCreery KM, Rossman SN, Wilson P, Wu TG, Paysse EA. Quantification of incidental needle and suture contamination during strabismus surgery. Binocul Vis Strabismus Q. 2003;18(2):75-9.

Reference Type: BACKGROUND

PMID: 12765540 (View on PubMed)

Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update. Ophthalmology. 2002 Jan;109(1):13-24. doi: 10.1016/s0161-6420(01)00899-5.

Reference Type: BACKGROUND

PMID: 11772573 (View on PubMed)

Davis GH, Finlayson N, Kemp R. Dilution of povidone-iodine. Med J Aust. 1985 Sep 30;143(7):321. doi: 10.5694/j.1326-5377.1985.tb123038.x. No abstract available.

Reference Type: BACKGROUND

PMID: 4046931 (View on PubMed)

Dereklis DL, Bufidis TA, Tsiakiri EP, Palassopoulos SI. Preoperative ocular disinfection by the use of povidone-iodine 5%. Acta Ophthalmol (Copenh). 1994 Oct;72(5):627-30. doi: 10.1111/j.1755-3768.1994.tb07191.x.

Reference Type: BACKGROUND

PMID: 7887164 (View on PubMed)

Ferguson AW, Scott JA, McGavigan J, Elton RA, McLean J, Schmidt U, Kelkar R, Dhillon B. Comparison of 5% povidone-iodine solution against 1% povidone-iodine solution in preoperative cataract surgery antisepsis: a prospective randomised double blind study. Br J Ophthalmol. 2003 Feb;87(2):163-7. doi: 10.1136/bjo.87.2.163.

Reference Type: BACKGROUND

PMID: 12543744 (View on PubMed)

Grimes SR, Hollsten D, Nauschuetz WF, Whiddon RG, Trevino SB. Effect of povidone-iodine irrigation on the preoperative chemical preparation of the eye. Mil Med. 1992 Mar;157(3):111-3.

Reference Type: BACKGROUND

PMID: 1603399 (View on PubMed)

Katosova LK. [The features of Haemophilus influenza and Streptococcus pneumoniae carriage and the comparative characteristics of strains isolated from healthy children and from patients with acute and chronic respiratory infections]. Zh Mikrobiol Epidemiol Immunobiol. 1994 Aug-Sep;Suppl 1:55-60. Russian.

Reference Type: BACKGROUND

PMID: 7856352 (View on PubMed)

Khashu M, Chessex P, Chanoine JP. Iodine overload and severe hypothyroidism in a premature neonate. J Pediatr Surg. 2005 Feb;40(2):E1-4. doi: 10.1016/j.jpedsurg.2004.10.028.

Reference Type: BACKGROUND

PMID: 15750908 (View on PubMed)

Lacey RW, Catto A. Action of povidone-iodine against methicillin-sensitive and -resistant cultures of Staphylococcus aureus. Postgrad Med J. 1993;69 Suppl 3(818):S78-83.

Reference Type: BACKGROUND

PMID: 8290463 (View on PubMed)

Mino de Kaspar H, Chang RT, Singh K, Egbert PR, Blumenkranz MS, Ta CN. Prospective randomized comparison of 2 different methods of 5% povidone-iodine applications for anterior segment intraocular surgery. Arch Ophthalmol. 2005 Feb;123(2):161-5. doi: 10.1001/archopht.123.2.161.

Reference Type: BACKGROUND

PMID: 15710810 (View on PubMed)

Olitsky SE, Vilardo M, Awner S, Reynolds JD. Needle sterility during strabismus surgery. J AAPOS. 1998 Jun;2(3):151-2. doi: 10.1016/s1091-8531(98)90006-4.

Reference Type: BACKGROUND

PMID: 10532751 (View on PubMed)

Prince HN, Nonemaker WS, Norgard RC, Prince DL. Drug resistance studies with topical antiseptics. J Pharm Sci. 1978 Nov;67(11):1629-31. doi: 10.1002/jps.2600671134.

Reference Type: BACKGROUND

PMID: 712607 (View on PubMed)

Recchia FM, Baumal CR, Sivalingam A, Kleiner R, Duker JS, Vrabec TR. Endophthalmitis after pediatric strabismus surgery. Arch Ophthalmol. 2000 Jul;118(7):939-44.

Reference Type: BACKGROUND

PMID: 10900107 (View on PubMed)

Roberts SM, Severin GA, Lavach JD. Antibacterial activity of dilute povidone-iodine solutions used for ocular surface disinfection in dogs. Am J Vet Res. 1986 Jun;47(6):1207-10.

Reference Type: BACKGROUND

PMID: 3729119 (View on PubMed)

Singer TR, Isenberg SJ, Apt L. Conjunctival anaerobic and aerobic bacterial flora in paediatric versus adult subjects. Br J Ophthalmol. 1988 Jun;72(6):448-51. doi: 10.1136/bjo.72.6.448.

Reference Type: BACKGROUND

PMID: 3390421 (View on PubMed)

Speaker MG, Milch FA, Shah MK, Eisner W, Kreiswirth BN. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology. 1991 May;98(5):639-49; discussion 650. doi: 10.1016/s0161-6420(91)32239-5.

Reference Type: BACKGROUND

PMID: 2062496 (View on PubMed)

Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with topical povidone-iodine. Ophthalmology. 1991 Dec;98(12):1769-75. doi: 10.1016/s0161-6420(91)32052-9.

Reference Type: BACKGROUND

PMID: 1775308 (View on PubMed)

Zamora JL. Chemical and microbiologic characteristics and toxicity of povidone-iodine solutions. Am J Surg. 1986 Mar;151(3):400-6. doi: 10.1016/0002-9610(86)90477-0.

Reference Type: BACKGROUND

PMID: 3513654 (View on PubMed)

Zamora JL, Price MF, Chuang P, Gentry LO. Inhibition of povidone-iodine's bactericidal activity by common organic substances: an experimental study. Surgery. 1985 Jul;98(1):25-9.

Reference Type: BACKGROUND

PMID: 4012604 (View on PubMed)

Other Identifiers

ABR 14357

Identifier Type: -

Identifier Source: org_study_id