Partial oral antibiotic treatment for bacterial brain abscess: An open-label randomised non-inferiority trial (ORAL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aalborg University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

2 May 2021 → ongoing

Decision date (initial)

2023-07-28

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Novo Nordisk Foundation

External identifiers

EU CT number

2023-505483-11-00

EudraCT number

2019-002845-39

ClinicalTrials.gov

NCT04140903

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine whether oral antibiotics are non-inferior (margin 10%) to IV antibiotics for bacterial brain abscess assessed by numbers meeting a primary, objective endpoint at 6 months after randomisation

Secondary objectives 1

1. To determine the proportions of patients with favourable outcome and all-cause mortalities during 1 year of follow-up, completion of allocated treatment (oral or IV), safety, and quality of life assessed by secondary endpoints

Conditions and MedDRA coding

Brain abscess

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age >17 years
2. Clinical presentation and brain imaging consistent with brain abscess
3. The physician in charge decides to treat the patient for brain abscess
4. Able to absorb oral medications
5. To have received guideline recommended intravenous antimicrobials for at least 14 consecutive days or longer before randomisation and no additional aspiraiton or excision of brain abscess planned.
6. Expected to be treated for at least another 14 days after randomisation.
7. No progression in neurological deficits or new-onset neurological symptoms (excluding seizures) within 5 days before randomisation

Exclusion criteria 10

1. Hypersensitivity to the intended antimicrobial with no other alternative drugs available
2. Expected substantially reduced compliance with treatment
3. Pregnancy (confirmed by urine or plasma human chorionic gonadotropin test in fertile women)
4. Lactating women
5. Concomitant treatment for proven or suspected CNS infection caused by mycobacteria, nocardia spp., pseudomonas spp., fungi, toxoplasmosis, or other CNS parasites
6. Device related brain abscesses (e.g. deep brain stimulators, ventriculo-peritoneal shunts)
7. Severe immuno-compromise defined as ongoing need for biological- or chemotherapy, prednisolone >20 mg/day for >14 days, uncontrolled HIV/AIDS, haematological malignancies, and organ transplant recipients
8. Concomitant or unrelated infections requiring >7 days of intravenous antimicrobials
9. Previous enrolment into this trial
10. Patients not capable of providing informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 6-month risk of death, rupture of brain abscess, unplanned aspiration or excision of brain abscess, relapse, or recurrence.

Secondary endpoints 11

1. Occurence of each component of the primary composite endpoint after 6 months since randomisation
2. All-cause mortality at 3-, 6-, and 12-months after randomisation
3. Unfavourable outcome at end of treatment as well as 3-, 6-, and 12-months since randomisation using sliding dichotomy of E-GOS stratified by level of comorbidity at time of randomisation
4. Completion and adherence to assigned treatment strategy
5. Line complications
6. Durations of admission and antibiotic treatment for brain abscess
7. Number of readmissions within 6 months since randomisation
8. Occurrence of Clostridioides difficile associated diarrhoea during brain abscess treatment
9. Oedema on cranial imaging at 3 months since randomisation.
10. Severe adverse events during brain abscess treatment
11. Quality of life scores and cognitive evaluations (SF-36, EQ-5D-5L, MoCA) at time of randomisation, end of treatment and 3-, 6-, and 12-months since randomisation

Investigational products

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

Test 5

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aalborg University Hospital

Sponsor organisation

Aalborg University Hospital

Address

Moelleparkvej 4

City

Aalborg

Postcode

9000

Country

Denmark

Scientific contact point

Organisation

Aalborg University Hospital

Contact name

Jacob Bodilsen

Public contact point

Organisation

Aalborg University Hospital

Contact name

Jacob Bodilsen

Third parties 1

Locations

4 EU/EEA countries · 29 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 29 files

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

Application history

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