Safety and Efficacy of Thermosensitive Hydroxybutyl Chitosan and 5-fluorouracil Assisted Endoscopic Dacryocystorhinostomy in the Treatment of Chronic Dacryocystitis

Endoscopic dacryocystorhinostomy (En-DCR) has the advantages of less surgical trauma, shorter time, less postoperative bleeding, faster recovery, and no skin scars. However, the success rate of En-DCR surgery still varies greatly between 58% and 94% , and the main reason for the failure of the surgery is the membranous closure of the anastomosis. The application of new packing materials in dacryocystorhinostomy provides some new ways to improve the success rate of En-DCR.

Hydroxybutyl chitosan (HBCS), with its non-toxicity, biocompatibility, biodegradability, antibacterial, moisturizing properties, water solubility and temperature sensitivity, is widely used in biomedicine to prevent postoperative adhesions.

5-Fluorouracil (5-FU) is an antimetabolite drug that is effective in the treatment of keloids. The application of 5-FU in glaucoma filtration surgery has demonstrated its good safety and efficacy. Studies have shown that antimetabolites as adjuvant therapy for DCR have a positive impact on improving the success rate of surgery In this study, thermosensitive hydroxybutyl chitosan will be applied to the anastomosis site of the nasal mucosal flap and the lacrimal mucosal flap, or 0.3ml of 5-fluorouracil solution (25mg/ml) was injected into the nasal mucosa around the anastomosis at the same time. The investigators would like to observe the different situations of clinical symptoms, lacrimal duct flushing, endoscopy, and bacterial flora changes in patients with chronic dacryocystitis, to compare them with the previous intraoperative packing of gelatin sponge wrapped with thrombin and Tobramycin Dexamethasone. Furthermore, the investigators intend to evaluate the safety and efficacy of HBCS and 5-FU adjuvant internal En-DCR in the treatment of chronic dacryocystitis, and provide new ideas for the adjuvant therapy of En-DCR.

Study Overview

• Status: Completed
• Conditions: Dacryocystorhinostomy; Fluorouracil; Hydroxybutyl Chitosan; Chronic Dacryocystitis
• Intervention / Treatment: Drug: Hydroxybutyl chitosan; Drug: 5-Fluorouracil; Drug: Gelatin Sponge Sheet

Detailed Description

Endoscopic dacryocystorhinostomy (En-DCR) has the advantages of less surgical trauma, shorter time, less postoperative bleeding, faster recovery, and no skin scars. However, the success rate of En-DCR surgery still varies greatly between 58% and 94% , and the main reason for the failure of the surgery is the membranous closure of the anastomosis. The application of new packing materials in dacryocystorhinostomy provides some new ways to improve the success rate of En-DCR.

Hydroxybutyl chitosan (HBCS), with its non-toxicity, biocompatibility, biodegradability, antibacterial, moisturizing properties, water solubility and temperature sensitivity, is widely used in biomedicine to prevent postoperative adhesions.

5-Fluorouracil (5-FU) is an antimetabolite drug that is effective in the treatment of keloids. The application of 5-FU in glaucoma filtration surgery has demonstrated its good safety and efficacy. Studies have shown that antimetabolites as adjuvant therapy for DCR have a positive impact on improving the success rate of surgery In this study, thermosensitive hydroxybutyl chitosan will be applied to the anastomosis site of the nasal mucosal flap and the lacrimal mucosal flap, or 0.3ml of 5-fluorouracil solution (25mg/ml) was injected into the nasal mucosa around the anastomosis at the same time. The investigators would like to observe the different situations of clinical symptoms, lacrimal duct flushing, endoscopy, and bacterial flora changes in patients with chronic dacryocystitis, to compare them with the previous intraoperative packing of gelatin sponge wrapped with thrombin and Tobramycin Dexamethasone. Furthermore, the investigators intend to evaluate the safety and efficacy of HBCS and 5-FU adjuvant internal En-DCR in the treatment of chronic dacryocystitis, and provide new ideas for the adjuvant therapy of En-DCR.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Limin Zhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Voluntary and able to sign an informed consent form
• Age ≥18 years
• Diagnosed with chronic dacryocystitis
• Willing and able to complete all planned visits and evaluations

Exclusion Criteria:

• Those who do not meet the inclusion criteria;
• Those who are allergic to hydroxybutyl chitosan and 5-fluorouracil;
• Patients suffering from blepharitis, hordeolum, blepharitis, ectropion, keratitis, lacrimal tumor and other external eye, ocular surface and other lacrimal diseases within three months, or those who have received eye surgery;
• Patients with chronic dacryocystitis and a history of lacrimal canal placement;
• Patients with history of lacrimal duct surgery and lacrimal duct fistula;
• Patients who have used glucocorticoid sprays within three months.
• Those who have had a history of facial trauma (eyelid trauma, nasal trauma, etc.) or have undergone facial surgery within three months;
• Abnormal nasal cavity or nasal diseases (nasal polyps, nasal tumors, turbinate hypertrophy, nasal bone fracture, etc.) within three months or those who have undergone nasal surgery;
• Patients with epiphora caused by other reasons such as facial paralysis or severe eyelid laxity;
• Those who suffer from autoimmune diseases, bleeding diseases, renal insufficiency dialysis treatment and other serious systemic diseases
• Patients with blisters or herpes zoster;
• Those with more serious skin diseases such as acne, rosacea or scar constitution;
• According to the investigator's judgment, it may interfere with Test results or medical history, personal history and allergy history that increase the risk of patients;
• Those who have participated in clinical trials of other drugs within the last 3 months;
• Those who cannot be followed up regularly or who cannot cooperate with the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBCS group; Apply HBCS to the anastomosis of the nasal mucosal flap and the dacryocyst mucosal flap	Drug: Hydroxybutyl chitosan; Apply HBCS to the anastomosis of the nasal mucosal flap and the dacryocyst mucosal flap
Experimental: HBCS+5-FU group; Inject 0.3ml of 5-FU solution (25mg/ml) into the nasal mucosa around the anastomosis, and apply HBCS to the anastomosis of the nasal mucosal flap and the dacryocyst mucosal flap	Drug: Hydroxybutyl chitosan; Apply HBCS to the anastomosis of the nasal mucosal flap and the dacryocyst mucosal flap; Drug: 5-Fluorouracil; Inject 0.3ml of 5-FU solution (25mg/ml) into the nasal mucosa around the anastomosis, and apply HBCS to the anastomosis of the nasal mucosal flap and the dacryocyst mucosal flap
Active Comparator: Gelatin Sponge group; Apply gelatin sponge sheet covered with thrombin and tobramycin and dexamethasone ophthalmic ointment to the anastomosis of nasal mucosal flap and dacryocyst mucosal flap	Drug: Gelatin Sponge Sheet; Apply gelatin sponge sheet covered with thrombin and tobramycin and dexamethasone ophthalmic ointment to the anastomosis of nasal mucosal flap and dacryocyst mucosal flap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical symptoms	postoperative comfort and bleeding, and epiphora using score sheets	six moths

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lacrimal duct flushing	Check for patency of the lacrimal drainage	six moths

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic examination	anastomotic areas(the lengths of the long and short axes), scarring and adhesions, and granulation	six moths
Bacterial flora changes	conjunctival sac, nasal mucosa	two moths

Collaborators and Investigators

• Sponsor: Tianjin Medical University Eye Hospital
• Investigators: Study Director: Zhu Li min, Tianjin medical university eye hosipital

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): December 3, 2023

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 14, 2023
• First Posted (Actual): December 19, 2023

Study Record Updates

• Last Update Posted (Actual): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Dacryocystitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hemostatics; Coagulants; Chelating Agents; Sequestering Agents; Fluorouracil; Chitosan
• Other Study ID Numbers: TianjinMUEH zlm

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