Parasitic Ulcer Treatment Trial Pilot

This is a study of optimal treatments for acanthamoeba keratitis. In the first part of the study, participants will be randomized to chlorhexidine monotherapy or chlorhexidine plus povidone iodine. After four weeks of therapy, participants will be re-randomized to early corticosteroids, later corticosteroids, or placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Acanthamoeba Keratitis
• Intervention / Treatment: Drug: Chlorhexidine; Drug: Povidone-Iodine; Drug: Prednisolone Sodium Phosphate; Drug: Prednisolone Sodium Phosphate; Drug: Hydroxypropyl Methylcellulose; Drug: Hydroxypropyl Methylcellulose

Detailed Description

Acanthamoeba keratitis is a rare eye infection that is difficult to treat. The mainstay of therapy is a biguanide agent such as chlorhexidine, though recent studies have found povidone iodine to be effective for killing acanthamoeba organisms in vitro. Thus, we randomize participants to topical chlorhexidine 0.04% monotherapy (i.e., routine care) versus topical chlorhexidine 0.04% plus topical poviodine iodine 2.5%. The primary outcome is clearance of acanthamoeba from the ocular surface at 4 weeks.

The role of topical corticosteroids in acanthamoeba keratitis is controversial. Topical corticosteroids can promote growth of acanthamoeba, but may also reduce inflammation and vision-threatening complications of infection. Here, we randomize participants who have completed a course of anti-amoebic therapy to one of three groups: early prednisolone sodium phosphate 1% (started at 4 weeks), late prednisolone sodium phosphate 1% (started at 6 weeks) or placebo (started at 4 weeks). The primary outcome will be visual acuity at 6 months.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jeremy D Keenan, MD; Phone Number: 415-476-1442; Email: jeremy.keenan@ucsf.edu
• Study Contact Backup: Name: Caitlin Moe, MPH; Phone Number: 415-502-2665; Email: caitlin.moe@ucsf.edu

Study Locations

• India
  • Tamil Nadu
    • Coimbatore, Tamil Nadu, India
      • Aravind Eye Hospital
    • Madurai, Tamil Nadu, India
      • Aravind Eye Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Trial 1 Inclusion Criteria:

• Smear or culture positive for acanthamoeba
• Age 13 years or greater

Trial 1 Exclusion Criteria:

• Interstitial or viral keratitis on history or examination
• Corneal perforation
• Therapeutic keratoplasty for acanthamoeba keratitis
• Unwillingness or inability to follow-up (e.g., living too far from hospital)

Trial 2 Inclusion Criteria

• Smear or culture positive for acanthamoeba, with 4 weeks of anti-amoebic treatment
• Age 13 years or greater
• Willing to participate in study

Trial 2 Exclusion Criteria

• Interstitial or viral keratitis on history or examination
• Fungus identified on culture and smear after 2 weeks of anti-amoebic treatment
• Corneal perforation
• Therapeutic keratoplasty for acanthamoeba keratitis
• Unwillingness or inability to follow-up (e.g., living too far from hospital)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chlorhexidine monotherapy; Topical chlorhexidine 0.04%	Drug: Chlorhexidine; 1 drop half-hourly for days 1-2, then hourly for days 3-6, then 8 times daily until the 4-week visit
Experimental: Chlorhexidine plus povidone iodine; Topical chlorhexidine 0.04% plus povidone iodine 2.5%	Drug: Chlorhexidine; 1 drop half-hourly for days 1-2, then hourly for days 3-6, then 8 times daily until the 4-week visit; Drug: Povidone-Iodine; 1 drop half-hourly for days 1-2, then hourly for days 3-6, then 8 times daily until the 4-week visit
Experimental: Early corticosteroids; Topical prednisolone sodium phosophate 1% for weeks 4-11	Drug: Prednisolone Sodium Phosphate; 1 drop 4 times daily for weeks 4-9, then 2 times daily for weeks 10-11; Drug: Prednisolone Sodium Phosphate; 1 drop 4 times daily for weeks 6-9, then 2 times daily for weeks 10-11
Experimental: Late corticosteroids; Artificial tears for weeks 4-5, then topical prednisolone sodium phosophate 1% for weeks 6-11	Drug: Prednisolone Sodium Phosphate; 1 drop 4 times daily for weeks 4-9, then 2 times daily for weeks 10-11; Drug: Prednisolone Sodium Phosphate; 1 drop 4 times daily for weeks 6-9, then 2 times daily for weeks 10-11; Drug: Hydroxypropyl Methylcellulose; 1 drop 4 times daily for weeks 4-9, then 2 times daily for weeks 10-11; Drug: Hydroxypropyl Methylcellulose; 1 drop 4 times daily for weeks 4-5
Placebo Comparator: Placebo; Artificial tears for weeks 4-11	Drug: Hydroxypropyl Methylcellulose; 1 drop 4 times daily for weeks 4-9, then 2 times daily for weeks 10-11; Drug: Hydroxypropyl Methylcellulose; 1 drop 4 times daily for weeks 4-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trial 1: Microbial clearance	Acanthamoeba culture	4 weeks
Trial 2: Best spectacle corrected visual acuity		6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Trial 1: Best spectacle corrected visual acuity	4 weeks
Trial 1: Time to re-epithelialization	4 weeks
Trial 1: Clinical cure	4 weeks
Trial 2: Time to clinical cure	6 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Research to Prevent Blindness
• Investigators: Principal Investigator: Jeremy D Keenan, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 24, 2018
• First Submitted That Met QC Criteria: March 24, 2018
• First Posted (Actual): March 30, 2018

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Eye Diseases; Parasitic Diseases; Protozoan Infections; Corneal Diseases; Eye Infections; Amebiasis; Eye Infections, Parasitic; Keratitis; Acanthamoeba Keratitis; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Disinfectants; Plasma Substitutes; Blood Substitutes; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Chlorhexidine; Povidone-Iodine; Povidone
• Other Study ID Numbers: UCSF-IRB-17-23895

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No