Multicentre randomised double-blind superiority trial with a roll-over phase to evaluate the efficacy of OM-89 vs placebo in reducing antibiotic consumption associated with the treatment of urinary tract infections in patients with a neurological bladder.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Dijon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

21 Nov 2024 → ongoing

Decision date (initial)

2024-08-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To compare the incidence rate of courses of antibiotics for urinary tract infections (administered to treat or prevent urinary tract infections) between M0 and M12 in patients with a spinal cord injury and a stabilised neurogenic bladder and on CIC, receiving either OM-89 (experimental group) or placebo (control group).

Secondary objectives 10

1. Compare between the experimental group and the control group :the incidence rate of urinary tract infections - febrile and non-febrile - at M12 and M24 (compared with M12)
2. Compare between the experimental group and the control group :the trend in the incidence of urinary tract infections over the two years of follow-up
3. Compare between the experimental group and the control group :hospitalisation rates for urinary tract infection at M12 and M24 (compared with M12), and changes in the hospitalisation rate over the two years of follow-up
4. Compare between the experimental group and the control group :rates of hospitalisation for sepsis with a urinary tract origin at M12 and M24 (compared with M12), as well as changes in the rate of hospitalisation for sepsis with a urinary tract origin over the two years of follow-up
5. Compare between the experimental group and the control group :the number of days on antibiotics (prescribed for urinary indications, and then for any indication) during the first and second years of follow-up, and changes over time, taking all antibiotics into account
6. Compare between the experimental group and the control group :the number of days on antibiotics (prescribed for urinary indications, then for any indication) during the first and second years of follow-up, and its evolution over time considering all antibiotics except those with a low ecological impact, namely oral fosfomycin, nitrofurantoin and pivmecillinam.
7. Compare between the experimental group and the control group :the number of courses of antibiotics for urinary indications at M12 and M24 (compared with M12)
8. Compare between the experimental group and the control group :the number of courses of antibiotics for any indication at M12 and M24 (compared with M12).
9. Compare between the experimental group and the control group :the health-related quality of life of patients at M0, M6, M12, M18 and M24 and its evolution over time
10. Compare between the experimental group and the control group :the safety of long-term treatment with OM-89.

Conditions and MedDRA coding

neurogenic bladder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Person who has given written consent
2. Patient aged 18 years or older
3. Patient with a stabilised neurogenic bladder following spinal cord injury that has not progressed for more than 2 years and who has undergone a urodynamic examination in the last 2 years.
4. Patients using CIC (5 to 6 per day)
5. Patients who have received at least 6 courses of antibiotic treatment for UTIs in the 12 months prior to screening (whether for curative or prophylactic reasons)
6. Patients with a negative urine culture between screening visit and randomisation or treated with antibiotics for urinary decontamination prior to randomisation.

Exclusion criteria 20

1. Person who is not affiliated with the national health insurance system
2. Person subject to a measure of legal protection (guardianship, tutorship)
3. Person subject to a court order
4. Adults unable to express consent
5. Patients using a urinary drainage method other than CIC
6. Patients with urinary lithiasis at the time of inclusion (assessed by renal imaging in the previous year as part of routine management for patients with a history(s) of lithiasis or within 3 years for patients with no history)
7. Presence of an endo-urinary device (urinary prosthesis, ureteral stent)
8. Enterocystoplasty or irradiated bladder (past or present)
9. Known allergy or previous intolerance to the active substance or one of the excipients of OM-89 or placebo
10. Patient unable to collect information in a daily diary.
11. Patient unable to understand follow-up by telephone.
12. Patient treated with bacterial lysates (including OM-89) in the 6 months prior to randomisation
13. Unable or unwilling to stop prophylactic antibiotic therapy prior to randomisation
14. Patient with a known malignant tumour or neoplasia
15. Patient with an autoimmune disease
16. Patient treated with long-term or bolus corticosteroids, anti-CD20 and anti-rejection therapy in the 6 months prior to screening
17. Patient currently taking part in another study on an investigational device or drug related to urinary tract infections, or who has received another investigational treatment in the 30 days prior to screening.
18. Patients planning to move to another residence in the year following randomisation
19. Non-menopausal women who are not surgically sterile (bilateral oophorectomy or hysterectomy) AND pregnant, breast-feeding who are declare that they are planning to conceive at inclusion, or not using effective* contraception. * Contraceptive methods considered to be highly effective birth control methods when used consistently and correctly, with a failure rate of less than 1%. • Combined hormones (containing estrogen and progestin) contraception associated with ovulation inhibition: ●oral ●intravaginal ●transdermal •Progestin-only hormonal contraception combined with ovulation inhibition: ●oral ●injectable ●implantable •Intrauterine device (IUD) •Intrauterine hormone delivery system •Bilateral tubal occlusion •Vasectomized partner
20. Patient requiring ongoing or short-term prolonged antibiotic therapy (e.g. infected bedsore, etc.)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of antibiotic treatment episodes for UTIsper person-days at risk during the first year. An episode of treatment is defined as a single prescription of a given antibiotic, regardless of its intended duration (curative or prophylactic). A day at risk is defined as a follow-up day without antibiotic treatment

Secondary endpoints 10

1. Number of symptomatic urinary tract infections - febrile and non-febrile - at M12 and M24 (compared with M12)
2. Number of febrile urinary tract infections at M12 and M24 (compared with M12)
3. Number of hospitalisations for urinary tract infections at M12 and M24 (compared with M12)
4. Number of hospital admissions for sepsis with a urinary tract origin at M12 and M24 (compared with M12)
5. Number of days spent on antibiotics at M12 and M24 (compared with M12) : for urinary indications / for any indication
6. Number of days spent on antibiotics with a significant ecological impact at M12 and M24 (compared with M12)
7. Number of courses of antibiotics for urinary indications at M12 and M24 (compared to M12)
8. Number of courses of antibiotics, whatever the indication, at M12 and M24 (compared with M12).
9. Quality of life score assessed at M0, M6 and M12, M18 and M24, using the Qualiveen questionnaire.
10. Number of adverse events (AEs) and relationship to OM-89 : Grade 1 mild AE - Grade 2 Moderate AE - Grade 3 Severe AE - Grade 4 Life-threatening or disabling AEs - Grade 5 AE-related death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Dijon

Sponsor organisation

Centre Hospitalier Universitaire De Dijon

Address

1 Boulevard Jeanne D Arc, Bp 77908 Bp 77908

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

Chef de projets

Public contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

Chef de projets

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications