Intravesical Glycosaminoglycan Instillation and Urinary Tract Infection in Acute Spinal Cord Injury

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and feasibility of administering glycosaminoglycan (GAG) therapy, iAluRil®, intravesically in individuals with acute spinal cord injury (SCI), commencing within the first ten days of injury, to prevent early urinary tract infections.

Detailed Description
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iAluRil®, listed as a medical device on the Australian Therapeutic Goods Registry (ATGR), contains both hyaluronic acid and chondroitin sulphate. This trial utilises iAluRil® for the same clinical indication as it is listed for on the ATGR, i.e. to re-establish the glycosaminoglycan (GAG) layers of the urothelial vesical tissue in cases in which their loss can cause problems, such as recurrent urinary tract infection in neurologically intact populations, but in a specific and vulnerable patient population (acute SCI). The trial will demonstrate the safety and feasibility of providing a series of iAluRil® treatments in early acute SCI, and provide an indication of effectiveness to prevent early urinary tract infections (compared to current standard infection control), informing researchers about the suitability of conducting a large randomised controlled clinical trial with this intervention. An 'Intervention post-UTI' arm for eligible inpatients and outpatients with SCI who have significant recurrent UTIs, will allow equivalent data collection and observations, informing researchers about a trial to reduce UTI recurrence during sub-acute/chronic SCI. Additionally, these patients will self-administer iAluRil® treatments providing data on the feasibility of SCI patients self-administering iAluRil® treatments.

Official Title
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Intravesical Glycosaminoglycan Instillation Following Spinal Cord Injury and Early Urinary Tract Infections; Safety and Feasibility Study

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: iAluRil® intravesical instillations


Participation Criteria
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Eligibility Criteria
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Arm A & B Inclusion Criteria: - Patients hospitalised at Royal Perth Hospital (RPH) in Western Australia following first acute traumatic SCI (with any degree of neurological impairment) Arm A & B Exclusion Criteria: Admitted to a hospital outside of Western Australia following SCI (prior to RPH) Unable to commence intervention within 10 days post-SCI Bladder or urethral trauma on admission Known history of bladder cancer or other bladder pathology Known hypersensitivity to hyaluronic acid, sodium salt or sodium chondroitin sulphate Diagnosis of a symptomatic urinary tract infection prior to commencing treatment Pregnancy Previous neurological disorder Inability to provide own consent due to intellectual, mental or cognitive impairment Arm C Inclusion Criteria: Previous traumatic or non-traumatic (sudden onset) SCI Experience significant, recurrent UTIs (in the opinion of the treating Spinal / Urology Consultant Willing and able to partake in all study requirements Emptying bladder via intermittent catheterisation (self or carer administered) Arm C Exclusion Criteria: Bladder or urethral trauma Known history of bladder cancer or other bladder pathology Known hypersensitivity to hyaluronic acid sodium salt or sodium chondroitin sulphate Pregnancy Previous neurological disorder Inability to provide own consent due to intellectual, mental or cognitive impairment Significant known history of Autonomic Dysreflexia associated with urological procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Consenting participants meeting eligibility criteria will join the intervention arm of trial; participants not meeting eligibility criteria and/or unwilling to receive intervention but consenting for data collection on bladder health measures for the study duration will join the non-intervention (standard care only) arm of trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Patients in this Arm will receive a series of seven iAluRil® intravesical instillations over a 12-week period as follows: Once per week for 4 weeks; then once every two weeks for 4 weeks; then once 4 weeks later. | Device: iAluRil® intravesical instillations<br>* 50ml of a sterile solution of sodium hyaluronate (1.6% 800mg/50ml) and sodium chondroitin sulphate (2% - 1 g/50ml) is administered intravesically (directly into the bladder) via a pre-filled syringe connected to a catheter and held in the bladder for at least 30 minutes.<br>* Other names: Intravesical glycosaminoglycan (GAG) therapy;|
| No Intervention: Arm B<br>Patients in this Arm will receive usual bladder care only. | |
| Experimental: Arm C<br>Patients in this Arm will be Spinal Urology Outpatients or Inpatients who are eligible for inclusion and experiencing significant urinary tract infection recurrence and/or complications. Patients will receive a series of seven iAluRil® intravesical instillations over a 12-week period as follows: Once per week for 4 weeks; then once every two weeks for 4 weeks; then once 4 weeks later. Patients will be encouraged and supervised to self-administer iAluRil® intravesical instillations. | Device: iAluRil® intravesical instillations<br>* 50ml of a sterile solution of sodium hyaluronate (1.6% 800mg/50ml) and sodium chondroitin sulphate (2% - 1 g/50ml) is administered intravesically (directly into the bladder) via a pre-filled syringe connected to a catheter and held in the bladder for at least 30 minutes.<br>* Other names: Intravesical glycosaminoglycan (GAG) therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of eligible traumatic SCI patients who start iAluRil within 10 days post injury | The proportion of eligible traumatic SCI patients who were urinary tract infection (UTI) free, able to provide informed consent and receive the first iAluRil instillation within 10 days of SCI | 10 days pos-SCI for each participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of eligible traumatic SCI patients administered iAluRil within 10 days of SCI who completed seven iAluRil instillations as per protocol over 12 weeks | The proportion of eligible traumatic SCI patients administered iAluRil within 10 days who then completed seven iAluRil instillations as per protocol over 12 weeks | 12 weeks (+/- 1 week) following recruitment for each participant | 
| Median time to first symptomatic UTI | Median time (days) between SCI and first medically diagnosed symptomatic UTI | Date of SCI to date of hospital discharge, an average of three months | 
| Incidence of symptomatic UTI/100 patient days | Number of medically diagnosed symptomatic UTIs per 100 days of hospitalisation | Date of SCI to date of hospital discharge, an average of three months | 
| Incidence of other urological complications/100 patient days | Number of other (non-UTI) urological complications per 100 days of hospitalisation | Date of SCI to date of hospital discharge, an average of three months | 
| Length of hospital stay | Number of days of initial hospitalisation (acute and subacute/rehabilitation) | Date of SCI to date of hospital discharge, an average of three months | 
| Bladder-related quality of life - bladder management difficulties | Validated SCI-QOL Questionnaire: 'Bladder Management Difficulties SF8a' | Conducted at 12 weeks post recruitment and at 24 weeks post recruitment for each participant | 
| Bladder-related quality of life - bladder complications | Validated SCI-QOL Questionnaire: 'Bladder Complications' | Conducted at 12 weeks post recruitment and at 24 weeks post recruitment for each participant | 
| Incidence of Adverse Events | Incidence of significant adverse events requiring medical intervention and/or impacting on hospital length of stay in Arm A will be described | During 12-week intervention period for each participant |