Parasitic Ulcer Treatment Trial (PUTT)

The Parasitic Ulcer Treatment Trial (PUTT) is a multi-center, parallel-group, randomized clinical trial. The purpose of this study is to determine whether including topical corticosteroids in a regimen for acanthamoeba keratitis (AK) will improve vision. Patients presenting to all enrollment centers with evidence of acanthamoeba keratitis will be eligible for the trial if there is evidence of ocular inflammation after 4 weeks of anti-amoebic therapy. Those who agree to participate will be randomized to one of two treatment groups:

• Group 1: Topical corticosteroid
• Group 2: Topical placebo

Study Overview

• Status: Recruiting
• Conditions: Acanthamoeba Keratitis
• Intervention / Treatment: Drug: Polyhexamethylene biguanide (PHMB); Drug: Topical corticosteroid; Other: Topical placebo

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jeremy Keenan, MD, MPH; Phone Number: 415-476-6323; Email: jeremy.keenan@ucsf.edu
• Study Contact Backup: Name: Krisi Aromin; Email: krisianne.aromin@ucsf.edu

Study Locations

• Brazil
  • São Paulo, Brazil
    • Recruiting
    • Federal University of São Paulo
    • Contact: Denise de Freitas
• India
  • Tamil Nadu
    • Coimbatore, Tamil Nadu, India
      • Recruiting
      • Aravind Eye Hospital
      • Contact: Revathi Rajamaran
    • Madurai, Tamil Nadu, India
      • Recruiting
      • Aravind Eye Hospital
      • Contact: NV Prajna
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Moorfields Eye Hospital
    • Contact: Su-yin Koay
• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California, San Francisco
      • Sub-Investigator: Gerami Seitzman, MD
      • Principal Investigator: Jeremy Keenan, MD, MPH
      • Contact: Krisianne Aromin; Email: krisianne.aromin@ucsf.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz
      • Contact: Travis Redd; Phone Number: 7208482020; Email: travis.redd@cuanschutz.edu
  • Florida
    • Gainesville, Florida, United States, 32605
      • Recruiting
      • University of Florida
      • Contact: Sonal Tuli
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: Guillermo Amescua
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois, Chicago
      • Contact: Elmer Tu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Mark Greiner
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
      • Contact: Nakul Shekhawat
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Leejee Suh
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
      • Contact: Travis Redd
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Bennie Jeng
    • Pittsburgh, Pennsylvania, United States, 15219
      • Recruiting
      • University of Pittsburgh Medical Center
      • Contact: Gaurav Prakash, MD; Phone Number: 412-647-2200; Email: prakashg@upmc.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Alejandro Arboleda, MD MS; Phone Number: 713-798-5143; Email: alejandro.arboleda@bcm.edu
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • University of Washington
      • Contact: Minh Nguyen, MD; Phone Number: 206-543-7250; Email: minhng88@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• AK on at least one of the following: culture, smear, PCR, shotgun sequencing, biopsy, or confocal microscopy
• Ocular inflammation after 1 month of anti-amoebic treatment, defined as conjunctival, corneal, episcleral, or anterior chamber inflammation

Exclusion Criteria:

• Evidence or history of interstitial keratitis
• Known herpetic keratitis, as determined from history, exam, or microbiological testing
• Known fungal keratitis, as demonstrated from corneal scrapings
• Corneal perforation or impending corneal perforation
• Prior therapeutic keratoplasty for acanthamoeba keratitis
• Unwillingness or inability to follow-up
• No light perception in the affected eye
• Known hypertensive response to steroids
• Corticosteroid allergy
• Concurrent treatment with systemic corticosteroids
• Concurrent granulomatous amoebic encephalitis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical steroids; Participants in this arm will receive anti-amoebic therapy plus topical steroids.	Drug: Polyhexamethylene biguanide (PHMB); PHMB is a cationic antiseptic agent used for topical treatment of acanthamoeba keratitis (AK). Both treatment groups will take PHMB at least 4 times daily while on the allocated study drug.; Other Names: Polyhexanide; Drug: Topical corticosteroid; Dexamethasone sodium phosphate, 0.1% ophthalmic solution will be administered 4 times daily for 4 weeks, then 2 times daily for 2 weeks, then 1 time daily for 2 weeks.
Placebo Comparator: Topical placebo; Participants in this arm will receive anti-amoebic therapy plus topical placebo.	Drug: Polyhexamethylene biguanide (PHMB); PHMB is a cationic antiseptic agent used for topical treatment of acanthamoeba keratitis (AK). Both treatment groups will take PHMB at least 4 times daily while on the allocated study drug.; Other Names: Polyhexanide; Other: Topical placebo; An artificial tear ophthalmic solution will be administered 4 times daily for 4 weeks, then 2 times daily for 2 weeks, then 1 time daily for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vision	Best corrected visual acuity	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Resolution	Time until clinical resolution (i.e., healed ocular surface and absence of inflammation)	12 months
Multivariate Analysis	The multivariate analysis will include the following outcomes measured at 6 months: best corrected visual acuity, corneal thinning on optical coherence tomography (OCT), scar density on Scheimpflug imaging, irregular astigmatism, glare, microbial clearance on confocal microscopy, pain score, time until clinical resolution	6 Months
Self-reported eye pain	Pain scale (Likert 11-point ordinal scale from 0 to 10; 0=no pain, 10=worst pain)	2 months

Collaborators and Investigators

• Sponsor: Jeremy Keenan, MD, MPH
• Collaborators: Johns Hopkins University; Baylor College of Medicine; University of Pennsylvania; University of Miami; Columbia University; National Eye Institute (NEI); University of Pittsburgh; University of Iowa; University of Illinois at Chicago; University of Florida; Oregon Health and Science University; Federal University of São Paulo; Moorfields Eye Hospital NHS Foundation Trust; Aravind Eye Care System; University of Colorado Denver - Anschutz Medical Campus (UCD-AMC)
• Investigators: Principal Investigator: Jeremy Keenan, MD, MPH, Proctor Foundation, UCSF; Principal Investigator: Gerami Seitzman, MD, Proctor Foundation, UCSF

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: steroids; corneal ulcer
• Additional Relevant MeSH Terms: Infections; Eye Diseases; Protozoan Infections; Parasitic Diseases; Corneal Diseases; Keratitis; Eye Infections; Eye Infections, Parasitic; Amebiasis; Corneal Ulcer; Acanthamoeba Keratitis; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenal Cortex Hormones; polihexanide
• Other Study ID Numbers: 23-39559; UG1EY033284 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD available on request.
• IPD Sharing Time Frame: After publication of the main results
• IPD Sharing Access Criteria: Request by email addressed to principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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