Povidone-iodine Antisepsis for Strabismus Surgery

Surgery Clinical Trial

— PASS  

Official title:

Prospective, Randomized, Double-blind Comparison of 5 % Against 1.25 % Povidone-iodine Solution as Preoperative Antisepsis for Strabismus Surgery in Young Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461656
• Other study ID #: ABR 14357
• Status: Completed
• Phase: Phase 4
• First received: April 17, 2007
• Last updated: March 4, 2013
• Start date: September 2009
• Est. completion date: December 2012

Study information

• Verified date: July 2011
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 5 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Endophthalmitis
• Strabismus
• Surgery

Intervention

Drug:
• 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%

Locations

Country	Name	City	State
Germany	Ernst Moritz Arndt University	Greifswald
Germany	Universitäts-Augenklinik	Magdeburg
Germany	Universitäts-Augenklinik Ludwig-Maximilian University	Munich
Netherlands	Dept. Ophthalmology Academical Medical Center	Amsterdam
Netherlands	Dept. Ophthalmology Free University Medical Center	Amsterdam
Netherlands	Dept. Ophthalmology	Leiden
Netherlands	Dept. of Ophthalmology St. Laurentius Ziekenhuis	Roermond
Netherlands	Dept. of Ophthalmology Erasmus Medical Center	Rotterdam
Netherlands	Rotterdam Eye Hospital	Rotterdam

Sponsors (9)

Lead Sponsor	Collaborator
Erasmus Medical Center	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Free University Medical Center, Laurentius Hospital Roermond, Leiden University Medical Center, Ludwig-Maximilians - University of Munich, Martin-Luther-Universität Halle-Wittenberg, Rotterdam Eye Hospital, University Medicine Greifswald

Countries where clinical trial is conducted

Germany,  Netherlands, 

References & Publications (25)

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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. — View Citation

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. — View Citation

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. — View Citation

Binder CA, Miño 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. German. — View Citation

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. — View Citation

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. — View Citation

Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update. Ophthalmology. 2002 Jan;109(1):13-24. Review. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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Khashu M, Chessex P, Chanoine JP. Iodine overload and severe hypothyroidism in a premature neonate. J Pediatr Surg. 2005 Feb;40(2):E1-4. — View Citation

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

Miño 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. — View Citation

Olitsky SE, Vilardo M, Awner S, Reynolds JD. Needle sterility during strabismus surgery. J AAPOS. 1998 Jun;2(3):151-2. — View Citation

Prince HN, Nonemaker WS, Norgard RC, Prince DL. Drug resistance studies with topical antiseptics. J Pharm Sci. 1978 Nov;67(11):1629-31. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with topical povidone-iodine. Ophthalmology. 1991 Dec;98(12):1769-75. — View Citation

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. — View Citation

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. — View Citation

Zamora JL. Chemical and microbiologic characteristics and toxicity of povidone-iodine solutions. Am J Surg. 1986 Mar;151(3):400-6. Review. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The difference in the mean numbers of bacterial colony forming units from pre-irrigation to post-irrigation with PI.		Cultures taken during surgery, evaluated within 2 days postoperatively	No
Secondary	Iodine excretion after surgery, assessed as urine iodine concentration per creatinine clearance.		24 hours postoperatively	No
Secondary	Postoperative erosion of the cornea and corneal oedema.		within 24 hours postoperatively	No