Au-Ag-Cu2O NG With PTT Anti Drug-resistant Microbial Keratitis

Gold-silver-cuprous Oxide (Au-Ag-Cu2O) Composite Nanogel Combined With Photothermal Therapy in the Treatment of Severe Drug-resistant Microbial Keratitis

This clinical study was conducted to evaluate the efficacy and safety of gold-silver cuprous oxide composite nanogels combined with photothermal therapy system in the treatment of severe drug-resistant bacterial keratitis ineffective by traditional antibiotic treatment in human eyes, and to provide translational applications. Based on the clinical evidence, a more effective and safe innovative treatment plan for corneal diseases has been developed.

Study Overview

• Status: Recruiting
• Conditions: Keratitis, Ulcerative; Antibiotic Resistance, Microbial; Photothermal Therapy
• Intervention / Treatment: Drug: Hollow gold and silver alloy cuprous oxide shell nano-shell hydrogel; Drug: Voriconazole eye drops; Other: Normal saline

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yue Qiao, PhD; Phone Number: +8619818504850; Email: qiaosensei@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Yue Qiao, PhD; Phone Number: +8619818504850; Email: qiaosensei@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The monocular cases of severe infectious keratitis admitted to our center were diagnosed as fungal keratitis according to their medical history, physical signs and surface secretions smear examination of corneal ulcer lesions (severe was defined as subjects with visual acuity < 0.15, deep stromal infiltration or involvement diameter >2mm, with extensive infiltration around or with extensive suppuration)
2. After more than 2 weeks of active treatment with antibiotics, there was no effect
3. The researchers communicated with the subjects in detail, and the subjects cooperated well and they voluntarily participated and signed informed consent

Exclusion Criteria:

1. Allergic to the drug in this test.
2. Pregnant and lactating women.
3. The medical history suggests serious heart, lung, liver, kidney dysfunction.
4. Patients with other factors that would affect the results of this result.
5. No signed informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nanogel photothermal therapy; After the subjects were enrolled in the study, the eyes were coated with Au-Ag-Cu2O nano-gel once (the concentration was 26.4μg/mL, the dosage was suitable to cover the ulcer surface evenly, and the dosage was recorded). Combined with mdl-n-808-10w near-infrared laser (China changchun new industry photoelectric technology) combined with photothermal therapy (laser wavelength 808 nm, power 1.5W/cm2, temperature controlled at 40℃, lasting 10min)	Drug: Hollow gold and silver alloy cuprous oxide shell nano-shell hydrogel; Hollow gold and silver alloy cuprous oxide shell nano-shell hydrogel was excited by NIR laser to release functional silver ions, copper ions and ROS.; Other Names: Au-Ag-Cu2O nano-gel
Active Comparator: Voriconazole eye drops; Voliconazole eye drops (once in half an hour) were also used in the control group.	Drug: Voriconazole eye drops; Voriconazole eye drops (1%) were administrated to infectious eye very frequently (once half an hour); Other Names: VRC
Placebo Comparator: Normal saline; Normal saline eye drops (once in half an hour) were also used in the control group.	Other: Normal saline; To be placebo, normal saline were administrated to infectious eye; Other Names: NS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anterior segment photography	corneal edema, keratohelcosis, hppopyon	1 month
confocal microscopy	fungal hyphae in corneal surface	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eye pressure	Measurement of contact tonometry with iCare TA01i tonometer after treatment (1 day, 1 week, 1 month)	1 month
visual acuity	Measurement of distance visual acuity with subjective refraction after treatment (1 week, 1 month)	1 month

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Director: Ke Yao, MD, Second Affiliated Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: February 9, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Photothermal Therapy; Keratitis, Ulcerative; Antibiotic Resistance, Microbial
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Eye Diseases; Corneal Diseases; Eye Infections; Ulcer; Keratitis; Corneal Ulcer; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Pharmaceutical Solutions; 14-alpha Demethylase Inhibitors; Ophthalmic Solutions; Voriconazole
• Other Study ID Numbers: 2021-0635

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No