Clinical trial NCT05180994: Topical Infliximab in Eyes With Penetrating Keratoplasty
Official title: Topical Infliximab in Eyes With Penetrating Keratoplasty
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glaucoma Following Surgery
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Fonds de recherche en ophtalmologie de l'Université de Montréal
name: Maisonneuve-Rosemont Hospital
name: Niagara Health System
name: Prism Eye Institute
name: Ottawa Hospital Research Institute
First posted: 2022-01-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Penetrating keratoplasty is a cornea surgery involving several inflammatory complications, of which the most important is glaucoma. Researchers wish to determine whether it is safe to administer infliximab (an anti-inflammatory drug) eye drops after surgery, and whether this eye drop could prevent the occurrence of glaucoma.

Detailed description: This is a prospective, multicenter, double-arm open clinical trial of 50 patients receiving a first penetrating keratoplasty (PKP) surgery, recruited to receive infliximab drops post-operatively.

The current study aims to evaluate whether using topical infliximab 10mg/ml eye drops is safe and efficient to prevent the emergence of glaucoma of inflammatory etiology in patients with PKP. This study is examining a new form of delivering infliximab (as eye drops instead of injections in the veins). 25 patients who will be undergoing PKP surgery will be recruited to receive infliximab drops as a part of this study.

The research hypothesis is that topical infliximab used during the PKP post-operative period will be safe, and could protect against the occurrence of glaucoma.

For comparison purposes, if some patients are not qualified to receive infliximab or should they refuse to receive infliximab, these patients will still be offered to follow the same follow-up schedule, questionnaires, examinations and non-invasive tests (excluding lab work), as patients who will be receiving infliximab. The number of patients in this control group will also be limited to 25 patients.

During the treatment period, patients in the interventional arm of the study will be receiving topical infliximab 10mg/ml eye drops four times per day, for a duration of 3 months. Patients will be monitored for another 3 months after cessation of the study drug. The total study duration for each patient will be 6 months.

Regarding statistical analysis, the primary and secondary outcomes of the study will be described, including : percentage of patients presenting with a thinning of mean retinal nerve fiber thickness measured using OCT (optical coherence tomography), with thinning in four quadrants (inferior, superior, nasal, temporal); proportion of patients without glaucoma over time; mean change in BCVA (best corrected visual acuity) compared to baseline BCVA; OSDI (Ocular Surface Disease Index) score evolution over time; quantification of ocular surface inflammation; quantification of anterior chamber inflammation; epithelial healing time; and incidence of epithelial keratitis.

Visual acuity values will be converted to LogMAR. Data will be presented as numbers and percentages for categorical variables, and as mean ± standard deviation for continuous variables. Comparison between experimental and comparison groups will be done using student's t test if distribution is parametric, and Mann-Whitney U test if distribution is non-parametric. The Kaplan-Meier curve will be used in order to illustrate the proportion of patients without glaucoma over time. An interim statistical analysis will be done once n=10 patients will have completed the full 6 months of study follow-up. A statistical significance level of α=0.05 will be used.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 80 years;
* First corneal transplant surgery;
* Capable of providing informed consent;
* Capable of administering eye medication or access to a caregiver able and willing to administer the eye medication for the patient.

Exclusion Criteria:

* Active ocular infection;
* Past corneal transplant (any technique);
* Advanced glaucoma or macular disease;
* Active or latent systemic infection (tuberculosis, histoplasmosis, coccidioidomycosis, cytomegalovirus, pneumocystis, aspergillosis or hepatitis B);
* Malignancy diagnosed in the past 5 years (any kind);
* Demyelinating disease;
* History or current diabetes mellitus (controlled or uncontrolled) or heart failure (New York Heart Association class III or IV);
* Pregnancy or breastfeeding;
* Allergy to infliximab or to a compound of its topical formulation;
* Significant anomaly of complete blood count or hepatic enzymes;
* Current or anterior use of anti-TNF-α medication or other anti-inflammatory biologics.

Primary outcomes:
measure: Complications associated to PKP surgery
timeFrame: 6 months
measure: Complications associated to infliximab use
timeFrame: 6 months
Secondary outcomes:
measure: Mean retinal nerve fiber thickness
timeFrame: 6 months
measure: Occurrence of glaucoma
timeFrame: 6 months
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: 6 months
measure: Ocular surface symptoms
timeFrame: 6 months
measure: Quantification of ocular surface inflammation
timeFrame: 6 months
measure: Quantification of anterior chamber inflammation
timeFrame: 6 months
measure: Epithelial healing time
timeFrame: 6 months
measure: Incidence of epithelial keratitis
timeFrame: 6 months
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: CHUM
name: Marie-Claude Robert, MD
role: PRINCIPAL_INVESTIGATOR
References: