Clinical trial NCT03945110: Intravesical Glycosaminoglycan Instillation and Urinary Tract Infection in Acute Spinal Cord Injury
Official title: Intravesical Glycosaminoglycan Instillation Following Spinal Cord Injury and Early Urinary Tract Infections; Safety and Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Spinal Cord Injuries
Lead sponsor: The University of Western Australia
Sponsor class: OTHER
Collaborators: name: Royal Perth Hospital
name: Fiona Stanley Hospital
name: Perth Urology Clinic
First posted: 2019-05-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of eligible traumatic SCI patients who start iAluRil within 10 days post injury
timeFrame: 10 days pos-SCI for each participant
Secondary outcomes:
measure: Proportion of eligible traumatic SCI patients administered iAluRil within 10 days of SCI who completed seven iAluRil instillations as per protocol over 12 weeks
timeFrame: 12 weeks (+/- 1 week) following recruitment for each participant
measure: Median time to first symptomatic UTI
timeFrame: Date of SCI to date of hospital discharge, an average of three months
measure: Incidence of symptomatic UTI/100 patient days
timeFrame: Date of SCI to date of hospital discharge, an average of three months
measure: Incidence of other urological complications/100 patient days
timeFrame: Date of SCI to date of hospital discharge, an average of three months
measure: Length of hospital stay
timeFrame: Date of SCI to date of hospital discharge, an average of three months
measure: Bladder-related quality of life - bladder management difficulties
timeFrame: Conducted at 12 weeks post recruitment and at 24 weeks post recruitment for each participant
measure: Bladder-related quality of life - bladder complications
timeFrame: Conducted at 12 weeks post recruitment and at 24 weeks post recruitment for each participant
measure: Incidence of Adverse Events
timeFrame: During 12-week intervention period for each participant
Other outcomes:
Locations:
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: The University of Western Australia
name: Sarah A Dunlop, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Damiano R, Cicione A. The role of sodium hyaluronate and sodium chondroitin sulphate in the management of bladder disease. Ther Adv Urol. 2011 Oct;3(5):223-32. doi: 10.1177/1756287211418723.
citation: Manas A, Glaria L, Pena C, Sotoca A, Lanzos E, Fernandez C, Riviere M. Prevention of urinary tract infections in palliative radiation for vertebral metastasis and spinal compression: a pilot study in 71 patients. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):935-40. doi: 10.1016/j.ijrobp.2005.09.016. Epub 2006 Jan 10.
citation: Damiano R, Quarto G, Bava I, Ucciero G, De Domenico R, Palumbo MI, Autorino R. Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial. Eur Urol. 2011 Apr;59(4):645-51. doi: 10.1016/j.eururo.2010.12.039. Epub 2011 Jan 18.
citation: King GK, Goodes LM, Hartshorn C, Thavaseelan J, Jonescu S, Watts A, Rawlins M, Woodland P, Synnott EL, Barrett T, Hayne D, Boan P, Dunlop SA. Intravesical hyaluronic acid with chondroitin sulphate to prevent urinary tract infection after spinal cord injury. J Spinal Cord Med. 2023 Sep;46(5):830-836. doi: 10.1080/10790268.2022.2089816. Epub 2022 Jul 6.