Intravesical LGG VS Saline Bladder Wash RCT

Official title

Intravesical Lactobacillus rhamnosusGG Versus Saline Bladder Wash: A Randomized, Controlled, Comparative Effectiveness Clinical Trial

Overview

This is the first ever comparative effectiveness study of an antibiotic-sparing novel self-management intervention to prevent complicated urinary tract infection (UTI).

Detailed description

Urinary tract infection (UTI) is the most common outpatient infection world-wide, and for people with spinal cord injury (SCI) and neurogenic bladder (NB), it is the most common infection, secondary condition, cause for emergency room visits, and infectious cause of hospitalization. Despite its prevalence, attempts to ameliorate UTI among people with SCI are stymied by long-standing diagnostic challenges which arise from evidence gaps around "gold standard" diagnostic tests (urinalysis and urine culture) that have lower sensitivity and specificity for UTI in this population. A high prevalence of chronic inflammation leading to persistence of white blood cells (WBC) in the urine confounds the utility of WBC count, pyuria, and leukocyte esterase as biomarkers for UTI; nitrites in urine indicate the presence of only specific (but not all) organisms, many of which are present to a greater extent in the urine of people with SCI; and people with SCI have a high prevalence of asymptomatic bacteriuria. These physiologic changes render the gold standard diagnostic tests less useful for identifying UTI in persons with SCI.

SPECIFIC AIM 1 Compare the effects of Lactobacillus Rhamnosus GG (LGG®) + Saline bladder wash (BW) versus BW alone on USQNB-determined bladder (B1) and urine quality (B2) symptom burden (two co-primary outcomes) where participants self-manage in response to two trigger symptoms (cloudier and/or more foul-smelling urine).

SPECIFIC AIM 2 Compare the effects of LGG®+BW versus BW alone (in response to the two trigger symptoms) on key secondary outcomes: number of days lost from rehabilitation, work, and/or school; number of days symptomatic; number of interactions with the health care system due to urinary symptoms; exposure to antibiotics (days, volume).

SPECIFIC AIM 3 Compare the prophylactic effects of LGG®+BW versus BW alone on USQNB-determined bladder (B1) and urine quality (B2) symptom burden.

SPECIFIC AIM 4 Compare the prophylactic effects of LGG®+BW versus BW alone on key secondary outcomes: number of days lost from rehabilitation, work, and/or school; number of days symptomatic; number of interactions with the health care system due to urinary symptoms; exposure to antibiotics (days, volume).

SPECIFIC AIM 5 Compare satisfaction of participants who instilled LGG®+BW to satisfaction of those who instilled BW only and determine if dropouts are differentially attributable to either intervention being perceived by participants as "not working".

Interventions

• Drug Lactobacillus RhamnosusGG
  LGG® (Culturelle Probiotic LGG®) will be used. This is the product we have used in the past and for which we have demonstrated safety, tolerability, and preliminary efficacy. For the LGG® instillation, participants will be instructed to mix the contents of 1 LGG® capsule into 45 cc sterile 0.9% saline. After mixing, participants will draw up the 45cc liquid LGG® mixture into a 60cc syringe and instill via the intermittent catheter after the last catheterization prior to going to bed. Participant
• Drug Saline bladder wash
  Participants will draw up the 45cc of normal saline into a 60cc syringe and instill via the intermittent catheter after the last catheterization prior to going to bed after trigger symptoms occur. Participants will be instructed to complete the USQNB-IC at the time of symptoms (in real time), and then continue completing the USQNB-IC at the determined frequency for the phase.

Primary outcome measures

• International SCI Lower Urinary Tract Function Basic Data Set [Time frame: Day 1]
• International SCI Core Data Set [Time frame: Day 1]
• NINDS Medical History CDE [Time frame: Day 1]
• NINDS Prior and Concomitant Medications CDE [Time frame: Day 1]
• Urinary Symptom Questionnaire for Neurogenic Bladder-Intermittent Catheter [Time frame: (SA1 and SA3) Weekly up to 18 months]
• Urinary Symptom Questionnaire for Neurogenic Bladder-Intermittent Catheter [Time frame: (SA1) Day 1 post-instillation (Phase 2: treatment phase)]
• Urinary Symptom Questionnaire for Neurogenic Bladder-Intermittent Catheter [Time frame: (SA1) Day 2 post-instillation (Phase 2: treatment phase)]
• Urinary Symptom Questionnaire for Neurogenic Bladder-Intermittent Catheter [Time frame: (SA3) Twice weekly post-instillation for up to 6 months (Phase 3: prophylaxis phase)]
• Patient Satisfaction Survey [Time frame: At final USQNB-IC completion (between 13 to 18 months) or at participant drop-out]

Eligibility criteria

Inclusion criteria

• Age ≥18 years;
• SCI at least 6 months duration;
• NLUTD (as determined by their SCI physician or urologist);
• Utilizing intermittent catheterization for bladder management; and
• Community dwelling (discharged from the acute care setting).

Exclusion criteria

• Known genitourinary pathology beyond neuropathic bladder (i.e., vesicoureteral reflux, bladder or kidney stones, etc.);
• Use of prophylactic antibiotics;
• Instillation of intravesical agents (e.g., gentamycin, saline; or Lactobacillus);
• Immunodeficiency;
• Any oral antibiotics within the past 2 weeks;
• Psychologic or psychiatric conditions influencing the ability to follow instructions;
• Participation in another study in which results would be confounded;
• 6 months since prior exposure to intravesical LGG®; and
• Active cancer (or within 5 years) or active autoimmune disorder

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• MedStar National Rehabilitation Hospital — Washington D.C.

Identifiers

NCT: NCT05230511 · STUDY00004287

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗