Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Partial Oral Antibiotic Treatment for Bacterial Brain Abscess (ORAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04140903
Recruitment Status : Not yet recruiting
First Posted : October 28, 2019
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Henrik Nielsen, Aalborg University Hospital

Brief Summary:
The investigators aim to determine if oral antibiotics are clinically acceptable as treatment of brain abscess. Following 2 weeks of standard intravenous antibiotic therapy, half of patients will continue with this treatment for another 4 weeks or longer while the other half will be assigned to oral antibiotics for the remaining duration of treatment.

Condition or disease Intervention/treatment Phase
Brain Abscess Cerebral Abscess Drug: Early transition to oral antibiotics Drug: Standard treatment of intravenous antibiotics Phase 4

Detailed Description:

Treatment of brain abscess remains a considerable challenge due to the precarious location of the infection and the impenetrability of the blood-brain-barrier for most drugs. Thus, cure usually requires a combination of neurosurgical evacuation of abscess material and 6-8 weeks of high-dose intravenous (IV) antibiotic therapy to ensure eradication of bacteria within the abscess cavity. Disadvantages include risks of nosocomial infections and line-associated complications (e.g. bleeding, venous thrombosis, or need for replacement due to malfunction) in addition to the considerable costs of such long-term admission. However, improved insights into the pharmacokinetic properties and favourable bioavailability of some oral antibiotics may allow such treatment at an early stage. To date, there are no randomised controlled trials to guide treatment of bacterial brain abscess.

The investigators wish to determine whether a treatment strategy of transition to oral antibiotics after two weeks of treatment is non-inferior to continued IV antibiotics in clinically stable brain abscess patients assessed by the proportion with a favourable outcome at six months since randomisation.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Investigator-initiated, international, multi-centre, randomised, parallel groups, non-inferiority trial
Masking: Single (Outcomes Assessor)
Masking Description: An independent blinded endpoint committee will assess the primary outcome.
Primary Purpose: Treatment
Official Title: Partial Oral Antibiotic Treatment for Bacterial Brain Abscess: An Open-label Randomised Non-inferiority Trial
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : August 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Abscess Antibiotics

Arm Intervention/treatment
Experimental: Oral antibiotics
Patients will be randomised to oral antibiotics after two weeks of appropriate antibiotic therapy for bacterial brain abscess since definitive aspiration/excision of brain abscess or, in case of no planned diagnostic neurosurgical procedure, since initiation of guideline recommended antibiotics for bacterial brain abscess
Drug: Early transition to oral antibiotics
Patients will be treated with an oral antibiotic regimen (e.g. amoxicillin + metronidazole) based upon pharmacokinetic and pharmacodynamic properties of the drugs, pathogen susceptibility, and any existing drug allergies or interactions

Active Comparator: Standard treatment
Patients will be randomised to continuation of standard intravenous antibiotics after two weeks of appropriate antibiotic therapy for bacterial brain abscess since definitive aspiration/excision of brain abscess or, in case of no planned diagnostic neurosurgical procedure, since initiation of guideline recommended antibiotics for bacterial brain abscess
Drug: Standard treatment of intravenous antibiotics
Patients will continue standard intravenous antibiotic therapy for brain abscess (e.g. 3rd generation cephalosporin + metronidazole) according to international guidelines and pathogen susceptibility patterns.




Primary Outcome Measures :
  1. Treatment failure [ Time Frame: Six months after randomisation ]
    A composite of number of participants with all-cause mortality, risk of intraventricular rupture of brain abscess (IVROBA), unplanned neurosurgery, relapse, or recurrence


Secondary Outcome Measures :
  1. Treatment failure [ Time Frame: At last day of antibiotic treatment for brain abscess, and 3- and 12-months after randomisation ]
    A composite of number of participants with all-cause mortality, risk of intraventricular rupture of brain abscess (IVROBA), unplanned neurosurgery, relapse, or recurrence

  2. Unfavourable outcome [ Time Frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation ]
    Number of participants with Extended Glasgow Outcome Scale score <7, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

  3. All-cause mortality [ Time Frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation ]
    Number of participants with fatal outcome, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

  4. Unplanned neurosurgery [ Time Frame: At 6 months since randomisation ]
    Number of participants with unplanned (re-)aspiration or excision, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

  5. IVROBA [ Time Frame: At 6 months since randomisation ]
    Number of participants with intraventricular rupture of brain abscess, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

  6. Relapse [ Time Frame: At 6 months since randomisation ]
    Number of participants with increase in brain abscess volume by 20% since randomisation, clinical deterioration attributable to brain abscess or lack of cure of at least 4 weeks or longer of assigned study treatment, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

  7. Recurrence [ Time Frame: At 6 months since randomisation ]
    New brain abscess formation after end of treatment, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)

  8. Unfavourable outcome - sliding dichotomy [ Time Frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation ]
    Sliding dichotomy of extended Glasgow Outcome Scale scores according to Charlson comorbidity index score (range: 0=no comorbidity and more likely to have a favourable outcome to 40=high degree of comorbidity with a poor prognosis of a favourable outcome) at time of randomisation (0 vs. 1-2 vs. >2).

  9. Central line associated complications [ Time Frame: 6 months since randomisation ]
    Number of participants with bleeding, infection, venous thrombosis or need for replacement of central line due to mechanical malfunction

  10. Clostridial diarrhea [ Time Frame: From randomisation up until last day antibiotic treatment for brain abscess ]
    Number of participants who develop Clostridioides difficile associated gastro-enteritis during antibiotic treatment for brain abscess

  11. Duration of admission [ Time Frame: From randomisation until hospital discharge to home or rehabilitation unit or death, whichever comes first, assessed up to 6 months ]
    Days spent as admitted patient in hospital up to 6 months since randomisation (does not include outpatient hospital care)

  12. Duration of treatment [ Time Frame: From randomisation until last day of antibiotic treatment for brain abscess up to 6 months since randomisation ]
    Number of days treated with antibiotics for brain abscess up to 6 months since randomisation

  13. Adherence to treatment [ Time Frame: From randomisation until last day of antibiotic treatment for brain abscess, assessed up to 6 months since randomisation ]
    Adherence to allocated treatment. For oral treatment this will be measured using Morisky 8-item Medication Adherence scale scores (range 0=high adherence to 8=low adherence) up to 6 months since randomisation

  14. Oedema on cranial imaging [ Time Frame: 3 months since randomisation ]
    Number of participants with residual perilesional oedema on cranial imaging up to 3 months since randomisation

  15. SAE [ Time Frame: From randomisation until last day of antibiotic treatment for brain abscess ]
    Number of participants with severe adverse events

  16. SF36 [ Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation ]
    Short Form 36 is a 36 item survey of patient-reported health-related quality of life (range 0=maximum disability to 100=no disability)

  17. EQ-5D-5L [ Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation ]
    EuroqQol - 5 dimensions - 5 level scores are derived from a standardized instrument for measuring generic health status including mobility, self-care, usual acitivities, pain/discomfort, and anxiety/depression (range 5=good health status to 25=poor health status)

  18. EQ-VAS [ Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation ]
    EuroqQol Visual Analogue Scale (range 0=poor health status to 100=excellent health status)

  19. Cognitive impairment [ Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation ]
    Montreal Cognitive Assessment (MoCA) scores (range 0=poor cognitive performance to 30=normal cognitive performance)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A clinical presentation (e.g. headache, neurological deficit or fever) and cranial imaging (CT or MRI) consistent with brain abscess AND
  2. The physician responsible for the patient decides to treat the patient for bacterial brain abscess AND
  3. Ability to take and absorb oral medications (including by nasogastric tube) AND
  4. To have received relevant antibiotic therapy for bacterial brain abscess for 14 consecutive days before randomisation AND
  5. Expected to be treated with antibiotic therapy for at least another 14 days after time of randomisation AND
  6. No progression in symptom intensity or occurrence of new-onset neurological symptoms (excluding seizures) within five days before time of randomisation.

Exclusion Criteria (patients fulfilling either criteria):

  1. Expected substantially reduced compliance with treatment (e.g. IV drug abuse)
  2. Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women <50 years of age)
  3. Concomitant (empirical) brain abscess treatment for tuberculosis, nocardiosis, Pseudomonas spp., fungi, toxoplasmosis or other CNS parasites
  4. Device related brain abscesses (e.g. deep brain stimulators, ventriculo-peritoneal shunts)
  5. Severe immuno-compromise defined as ongoing need for biological- or chemotherapy, prednisolone >20 mg/day for 14 days or longer, uncontrolled HIV/AIDS, haematological malignancies, and organ transplant recipients
  6. Concomitant or unrelated infections necessitating IV antibiotics beyond seven days of duration after time of randomisation
  7. Previous enrolment into this trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04140903


Contacts
Layout table for location contacts
Contact: Jacob Bodilsen, MD +45 97663920 jacob.bodilsen@rn.dk
Contact: Henrik Nielsen, Professor +45 97663920 henrik.nielsen@rn.dk

Sponsors and Collaborators
Henrik Nielsen
Investigators
Layout table for investigator information
Principal Investigator: Jacob Bodilsen, MD Aalborg University Hospital

Layout table for additonal information
Responsible Party: Henrik Nielsen, Professor, Aalborg University Hospital
ClinicalTrials.gov Identifier: NCT04140903    
Other Study ID Numbers: 1
First Posted: October 28, 2019    Key Record Dates
Last Update Posted: October 28, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Beginning six months and ending three years after publication, an anonymized dataset can be shared with qualified researchers who provide a methodologically sound proposal for a post-hoc study assessed by the members of the steering committee. The anonymized dataset will include baseline demographics of patients, laboratory results, treatments and primary outcome at six months since randomisation. In addition, the study protocol, statistical analysis plan, informed consent form, clinical study report and analytic code can also be shared. Proposals should be directed to the trial manager. To gain access, data requestors will need to sign a data access agreement. Data will be deposited at Mendeley Data (https://data.mendeley.com/).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 6 months until 3 years after publication
Access Criteria: Qualified researchers who provide a methodologically sound proposal for a post-hoc study assessed by the members of the steering committee may gain access to data after proper governmental approvals have been obtained.
URL: https://data.mendeley.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Henrik Nielsen, Aalborg University Hospital:
Oral antibiotics
Additional relevant MeSH terms:
Layout table for MeSH terms
Abscess
Brain Abscess
Suppuration
Infection
Inflammation
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents