Assessment of the effectiveness and safety of Bibrocathol 2% eye ointment (Bibrocathol-POS 2%) in the treatment of chronic blepharoconjunctivitis

ISRCTN ISRCTN14084351
DOI https://doi.org/10.1186/ISRCTN14084351
Submission date
03/02/2021
Registration date
08/03/2021
Last edited
09/09/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Eye Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aim
Blepharoconjunctivitis occurs when normal bacteria that live on the eyelid skin cause irritation and inflammation to the eyelids that spreads to the conjunctiva (the clear tissue covering the white part of the eye and the inside of the eyelids).
Bibrocathol is a well known antiseptic drug for the treatment of the signs and symptoms of chronic blepharoconjunctivitis, and is widely used in clinical practice. The aim of this study is to test the effectiveness and safety of Bibrocathol 2% eye ointment (Bibrocathol-POS 2%) in chronic blepharoconjunctivitis.

Who can participate?
Patients with chronic blepharoconjunctivitis may participate in this study if they do not yet require antibiotic treatment

What does the study involve?
The study includes four visits (screening, baseline, control assessment and final examination). The total duration of study for one patient is about 2-3 weeks. Eye examinations include measurement of visual acuity, intraocular pressure (the fluid pressure inside the eye), and slit-lamp biomicroscopy. A questionnaire is completed and physical examinations including blood pressure and weight measurement are performed at screening day. If applicable, a pregnancy test is carried out at screening. A patient diary is used to document the application of the investigational product by the patient.

What are the possible benefits and risks of participating?
The patient can benefit from bibrocathol and vehicle treatment or at least from the care and diagnostic supervision of the investigator. Eventually, it may be that there is no direct benefit from the participation in the study. However, participation in this study may possibly contribute to improved future treatment of other patients with the same or a comparable disease.

Where is the study run from?
URSAPHARM Arzneimittel GmbH (Germany)

When is the study starting and how long is it expected to run for?
November 2014 to October 2019

Who is funding the study?
URSAPHARM Arzneimittel GmbH (Germany)

Who is the main contact?
Dorothea Gross
d.gross@ursapharm.de

Contact information

Mrs Dorothea Groß
Scientific

Industriestrasse 35
Saarbrücken
66129
Germany

Phone +49 (0)6805 9292 132
Email dorothea.gross@ursapharm.de

Study information

Study designInterventional multi-centre randomized double-masked placebo-controlled parallel-group trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Other
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a participant information sheet
Scientific titleA multi-centre, randomized, double-masked, placebo-controlled, parallel-group, phase III study to assess efficacy and safety of Bibrocathol 2% eye ointment (Bibrocathol-POS 2%) in the treatment of chronic blepharoconjunctivitis
Study objectivesAssessment of a reduction in the signs and symptoms of chronic blepharoconjunctivitis.
Ethics approval(s)1. Approved 17/04/2017, Ethics Committee of Federal State Budgetary Educational Institution of Higher Education “Russian National Research Medical University n.a N.I. Pirogov” of the Ministry of Health of the Russian Federation (Ostrovityanova str. 1,117997, Moscow, Russian Federation; +7 (0)495 343 30 83; ek@rsmu.ru), ref: not available
2. Approved 10/04/2017, Ethics Committee of Federal State Budgetary Institution “Moscow Helmholtz Scientific Research Institute of Eye Diseases” of the Ministry of Healthcare of the Russian Federation (Sadovaya-Chernogryazskaya str. 14/19, 105062, Moscow, Russian Federation; +7 (0)495 623 41 61; info@igb.ru), ref: not available
3. Approved 17/05/2017, Ethics Committee of Federal State Budgetary Educational Institution of Higher Education “Saint Petersburg State Pediatric Medical University” of the Ministry of Healthcare of the Russian Federation (Litovskaya str. 2, 194100, Saint Petersburg, Russian Federation; +7 (0)812 295 9146; dogovor@gpma.ru), ref: not available
4. Approved 11/09/2017, Ethics Committee of Federal State Budgetary Educational Institution of Higher Education “Pavlov First Saint Petersburg State Medical University” of the Ministry of Healthcare of the Russian Federation (L’va Tolstogo str. 6/8, 197022, Saint Petersburg, Russian Federation; +7 (0)812 338 66-17; spbgmutrials@yandex.ru), ref: not available
5. Approved 26/05/2017, Local Ethics Committee of Regional Budgetary Healthcare Institution "Ivanovo Regional Clinical Hospital" (Luybimova str. 1, 153040, Ivanovo, Russia Federation; +7 (0)4932 56 22 48; email: not available), ref: not available
Health condition(s) or problem(s) studiedChronic blepharoconjunctivitis
InterventionPatients are randomized with a 1:1 (verum: placebo) allocation ratio. A strip of the investigational product (about 5 mm) is administered in the conjunctival sac and on the lower and upper eyelid in the morning, at noon, and in the evening for 2 weeks.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase III
Drug / device / biological / vaccine name(s)Bibrocathol 2% eye ointment (Bibrocathol-POS 2%); 4,5,6,7-Tetrabromo-1,3,2-benzodioxabismol-2-ol
Primary outcome measureSigns of chronic blepharoconjunctivitis, expressed as a sum score which comprises the severity of:
1. Lid oedema measured using slit-lamp examination at screening, day 1, day 7 and day 15
2. Lid erythema measured using slit-lamp examination at screening, day 1, day 7 and day 15
3. Debris measured using slit-lamp examination at screening, day 1, day 7 and day 15
4. Hyperemia measured using slit-lamp examination at screening, day 1, day 7 and day 15
5. Pouting of Meibomian glands assessed by the investigator at screening, day 1, day 7 and day 15
Secondary outcome measuresThe individual parameters:
1. Lid oedema measured using slit-lamp examination at screening, day 1, day 7 and day 15
2. Lid erythema measured using slit-lamp examination at screening, day 1, day 7 and day 15
3. Debris measured using slit-lamp examination at screening, day 1, day 7 and day 15
4. Hyperemia measured using slit-lamp examination at screening, day 1, day 7 and day 15
5. Pouting of Meibomian glands measured by investigator assessment at screening, day 1, day 7 and day 15
Overall study start date17/11/2014
Completion date28/10/2019

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants200 patients randomized (100 verum; 100 placebo)
Total final enrolment200
Key inclusion criteria1. Written informed consent
2. Ambulatory male and female patients ≥18 years of age
3. Diagnosis of chronic blepharoconjunctivitis
4. A summarised score of signs and symptoms (sum score of severity of lid oedema, lid erythema, debris, hyperemia and pouting of Meibomian glands and additionally the patient’s assessment of ocular discomfort) of ≥ 18 at baseline
5. Ability of the patient to cooperate (able to understand the provided information about the clinical trial, willing to comply with the requirements of the study protocol)
6. Consent to use adequate contraception
7. Women using adequate contraception with a negative pregnancy test (for women with childbearing potential), or women who had menopause 2 years before the start of the study or earlier
Key exclusion criteriaNon-inclusion criteria:
Ocular conditions:
1. Chronic blepharoconjunctivitis requiring antibiotic treatment
2. Therapy-resistant chronic blepharoconjunctivitis
3. Acute ocular and/or follicle or lid infection or active ocular inflammation other than blepharoconjunctivitis
4. Irritations of the outer eye that are related to corneal damage (e. g. erosions, injuries, burns)
5. Abnormal eyelid anatomy (other than due to chronic blepharoconjunctivitis)
6. Ocular surgery within 90 days (trauma, intraocular surgery, refractive surgery, palpebral surgery (e.g. ectopium OP), etc)
7. Severe dry eye syndrome also due to systemic diseases
8. Allergic eye disease
9. Glaucoma
10. IOP ≥21 mmHg (non-contact tonometry)
11. Patients with only one eye

Systemic condition:
12. Known hypersensitivity to the investigational product or any of the ingredients from the composition of the investigational product (or of placebo)
13. Severe systemic disease (incl. rheumatoid arthritis, ankylosing spondylitis)
14. Subjects with a history of malignancy of any organ system, treated or untreated, within the past 5 years, whether or not evidence of local recurrence or metastases exists

Concomitant medication:
15. Oral or topical antibiotics 2 weeks prior to and during the trial
16. Any other ocular antiseptics during the trial
17. Topical ocular or systemic corticosteroids 2 weeks prior to and during the trial (except chronic use of inhalative corticosteroids if on stable dose 1 month prior to and during the trial)
18. Topical ocular and systemic NSAIDs 2 weeks prior to and during the trial (low-dose oral acetylsalicylic acid and occasional use of painkillers is allowed)
19. Local ocular use of antihistamines 1 month and prior to and during the trial
20. Ocular α-sympathomimetics 1 month and prior to and during the trial

Other:
21. Patients who anticipate changes in their ongoing regimen of concurrent systemic therapies that could affect trial parameters
22. Pregnant or breastfeeding women
23. Women with childbearing potential, not using a reliable and medically accepted method of contraception (no pregnancy test is required in women, being 2 years after menopause)
24. Any systemic or ocular medical or physical condition which, in the investigator’s opinion, would preclude the participant from adhering to the protocol or completing the trial per protocol
25. Patients participating in another clinical trial at the same time
26. Patients taking any investigational product during the last 28 days
27. Patients already once included in this trial

Exclusion criteria:
1. Recall of the informed consent by the patient
2. Necessity to discontinue study treatment /placebo due to the occurrence of adverse events and/or exacerbation of concurrent diseases which prevent further participation in the study
3. Applicability of adjunctive therapy which is not permitted within this Protocol
4. Other conditions or events which require, in the physician's opinion, withdrawal of the patient from the study. If such a decision is taken based on adverse events related to intake of test medications or comparative medications, the Study Sponsor or its representatives shall be informed immediately
5. Non-performance of the case monitoring of the parameters specified in the Study Protocol
6. Intake/use by the patient of medications prohibited within this study
7. The patient’s nonobservance of the procedures prescribed by the Protocol
8. Administrative reasons (discontinuation of the study by the Sponsor or regulatory authorities), and gross violations of the Protocol with a potential to impact the findings
9. Any changes in performing lid hygiene during the study
10. Wearing of contact lenses during the study
Date of first enrolment15/01/2018
Date of final enrolment15/02/2019

Locations

Countries of recruitment

  • Russian Federation

Study participating centres

Federal State Budgetary Educational Institution of Higher Education “Russian National Research Medical University n.a N.I. Pirogov” of the Ministry of Health of the Russian Federation
Moscow
117997
Russian Federation
Federal State Budgetary Institution “Moscow Helmholtz Research Institute of Eye Diseases" of the Ministry of Healthcare of the Russian Federation
14/19, Sadovaya-Chernogryazskaya str.
Moscow
105062
Russian Federation
Federal State Budgetary Educational Institution of Higher Education “Saint Petersburg State Pediatric Medical University” of the Ministry of Healthcare of the Russian Federation
2 Litovskaya str.
Saint Petersburg
194100
Russian Federation
Federal State Budgetary Educational Institution of Higher Education "Pavlov First Saint Petersburg State Medical University" of the Ministry of Healthcare of the Russian Federation
6/8 L’va Tolstogo str.
Saint Petersburg
197022
Russian Federation
Regional Budgetary Healthcare Institution “Ivanovo Regional Clinical Hospital”
1 Luybimova str.
Ivanovo
153040
Russian Federation

Sponsor information

Funders

Funder type

Industry

URSAPHARM Arzneimittel GmbH

No information available

Results and Publications

Intention to publish date04/08/2021
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination plan1. Additional documents not available in web format, please use the contact details to request study-related material
2. Planned publication in a high-impact peer-reviewed journal
IPD sharing planThe datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article 17/05/2022 09/09/2022 Yes No

Editorial Notes

09/09/2022: Publication reference added.
04/02/2021: Trial's existence confirmed by the Local Ethics Committee of Regional Budgetary Healthcare Institution "Ivanovo Regional Clinical Hospital".