A randomized masked clinical trial to assess the efficacy of 1% Voriconazole ophthalmic solution compared to combined use of topical 0.02% Polyhexamethylene biguanide and 0.02% Chlorhexidine ophthalmic solutions in the treatment of Acanthameba keratitis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Treatment failure – failure to induce a favorable clinical response within two weeks of initiating therapy with either voriconazole or combined therapy.
研究概览
简要总结
Acanthamebakeratitis (AK) is a rare but potentially devastating amoebic infection of thecornea. A prevalence of 1.2 per million adults and 0.2 (United States) to 2(United Kingdom) per 10,000 soft contact lens wearers per year is reported1,2The increased incidence of Acanthameba keratitis in soft contactlens wear occurred with the use ofnon-sterile contact lens solutions and homemade saline tablets 1Theother causes of increased incidence are reported to contaminated municipalwater supplies 3andthe use of a widely available multipurpose contact lens disinfectingsolution 4 In India, Acanthamoeba is one of thecausative organisms of keratitis with no historyof contact lens usage.5
Currently,the management of Acanthamoebakeratitis is diamidines and biguanides which are cysticidal in vitro. Polyhexamethylene biguanide 0.02% (200–600g/ml) and chlorhexidine 0.2% are used in combination or as single drug therapy with diamidines ( Propamidine isethionate andhexamidine). 6,7The biguanides interact with the cytoplasmic membrane,resulting in loss of cellular components and inhibition of respiratory enzymes.The antimicrobial effects of the diamidines result from the cationic surfaceactive properties inducing structural membrane changes that affect cellpermeability. When these molecules penetrate into the amoebic cytoplasm,denaturation of cytoplasmic proteins and enzymes occurs. Propamidine andhexamidine have been clinically effective against both the trophozoite and cystforms of Acanthamoeba. Single drug use of diamidine can lead toresistance and should not be used as monotherapy. 8 Chlorhexidine has been shown to beeffective against Acanthamoeba.6,9 Oral Voriconazole as monotherapy has been shown tobe effective in the treatment of refractory AK. 10Good penetration of topical voriconazolehas been shown in a recent study wherein the aqueous humor concentration was0.61-3.30 mg/L after one hour of topical administration in fungal keratitis. 11Astrong inhibitory effect upon Acanthamoebaspp. and N. fowleri at all drugconcentrations through 40 microg/ml hasbeen reported with voriconazole12.These studies are either in vitro or reported as case series. 12-14Tuet al have shown the clinical resolution of AK with oral monotherapy ofVoriconazole. 10
研究设计
- 研究类型
- Interventional
- 分配方式
- Random Number Table
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Age equal to or more than 18 years.
- •Male or female 3) Stromal infiltrate size between 2-6 mm.
- •Corneal scraping positive for Acanthamoeba cysts in direct smear examination by any one or more of the methods used.
排除标准
- •The corneal scrapings are negative for Acanthamoeba.
- •The patient has a history of allergy to voriconazole or chlorhexidine 3) The cornea or sclera has been perforated or perforation is impending.
- •The unaffected eye is legally blind.
- •The patient is known to be HIV positive or diabetic.
- •The initial culture shows significant growth of bacteria (>10 colonies) or fungus.
- •Both eyes are infected.
结局指标
主要结局
Treatment failure – failure to induce a favorable clinical response within two weeks of initiating therapy with either voriconazole or combined therapy.
时间窗: 2 weeks
次要结局
- Time to healing, visual acuity change, scar(2 weeks)