Bacteriuria
Conditions
Brief summary
Urinary tract infection (UTI) is the most common infection in nursing home residents, and bacteriuria is the greatest trigger for antimicrobial therapy in the nursing home setting. The primary aim of this study is to test the efficacy of two oral cranberry capsules per day in the reduction of bacteriuria plus pyuria in female nursing home residents. These aims will be accomplished by conducting a double blind randomized placebo controlled efficacy trial of two oral cranberry capsules daily versus placebo in a cohort of Connecticut female nursing home residents.
Interventions
DIETARY_SUPPLEMENT2 cranberry capsules
Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC)
DIETARY_SUPPLEMENTPlacebo
Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC)
Sponsors
National Institute on Aging (NIA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants were randomized to cranberry or placebo capsules.
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. female residents; 2. long term residents 3. English speaking; and 4. age ≥ 65 years.
Exclusion criteria
1. residents that are not expected to be in the nursing home for at least one month (i.e., short term rehabilitation, pending discharge, terminal \[life expectancy \< 1 month\]); 2. residents who are on chronic suppressive antibiotic or anti-infective (i.e., mandelamine) therapy for recurrent UTI; 3. residents with end stage renal disease on dialysis (they do not regularly produce urine); 4. residents unable to produce a baseline clean catch urine specimen for collection; 5. residents on warfarin therapy because of a potential interaction of warfarin and cranberry juice; 6. residents with a history of nephrolithiasis because cranberry may increase the risk of nephrolithiasis; 7. have an indwelling bladder catheter in place; 8. have an allergy to cranberry products; 9. are being treated with cranberry products; 10. residence \<4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | One year | Clean catch urine cultures and urinalyses will be obtained every two months for each participant for study purposes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Episodes of Symptomatic UTI | One year | Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met. |
| Number of Hospitalizations | One year | — |
| Number of Deaths | One year | — |
| Number of Antibiotic Prescriptions | One year | Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant. |
| Number of Antibiotic Prescriptions for Suspected UTI | One Year | Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant's suspected UTI. |
| Subjects With 1, 2, or 3 Episodes of UTIs | One year | Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met. |
| Bacteriuria With Multidrug-resistant Gram-negative Bacilli | One year | All urine culture data will be reviewed to determine presence of multidrug-resistant gram-negative bacilli (resistance to ≥3 of the following antibiotics: ampicillinsulbactam,cefazolin, ceftriaxone, ceftazidime, fluoroquinolones, piperacillin-tazobactam, meropenem, imipenem, and trimethoprim-sulfamethoxazole). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events in Participants | One year | — |
| Adherence to Capsule Intake by All Participants | One year | measured by capsules removed from blister packs |
Countries
United States
Participant flow
Recruitment details
Recruited from nursing homes within 50 miles of New Haven.
Pre-assignment details
806 patients were eligible, 558 declined to participate. Of the 248 consented, 63 were found to be ineligible after consent, leaving 185 to randomize.
Participants by arm
| Arm | Count |
|---|---|
| 2 Cranberry Capsules Experimental: 2 cranberry capsules
2 cranberry capsules: Two cranberry capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | 92 |
| 2 Placebo Capsules Experimental: 2 placebo capsules qd
Placebo: Two placebo capsules qd (each capsule containing 36mg proanthocyanidin, total 72mg PAC) | 93 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 17 | 16 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Total | 2 Cranberry Capsules | 2 Placebo Capsules |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 185 Participants | 92 Participants | 93 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Bacteriuria plus pyuria | 59 participants | 27 participants | 32 participants |
| Race/Ethnicity, Customized Non-White | 18 Participants | 9 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 167 Participants | 83 Participants | 84 Participants |
| Sex: Female, Male Female | 185 Participants | 92 Participants | 93 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 92 / 92 | 93 / 93 |
| serious Total, serious adverse events | 50 / 92 | 66 / 93 |
Outcome results
Primary
Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC)
Clean catch urine cultures and urinalyses will be obtained every two months for each participant for study purposes.
Time frame: One year
Population: 147 subjects completed 1 year, 33 died. 20 subjects, 9 in the treatment group v 11 in the control group, became incontinent prior to the first time point, thus unable to provide any urine. 45 subjects stopped taking the capsules, 24 in treatment and 21 in control; 21 refused, 19 transitioned to hospice, 4 started warfarin, and 1 refused via family.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2 Cranberry Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 4 months | 15 participants |
| 2 Cranberry Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 8 months | 14 participants |
| 2 Cranberry Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 2 months | 21 participants |
| 2 Cranberry Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 10 months | 15 participants |
| 2 Cranberry Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 6 months | 13 participants |
| 2 Cranberry Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 12 months | 12 participants |
| 2 Cranberry Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | Baseline | 26 participants |
| 2 Placebo Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 12 months | 9 participants |
| 2 Placebo Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | Baseline | 32 participants |
| 2 Placebo Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 2 months | 27 participants |
| 2 Placebo Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 4 months | 26 participants |
| 2 Placebo Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 6 months | 20 participants |
| 2 Placebo Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 8 months | 14 participants |
| 2 Placebo Capsules | Participants With Urine Cultures With Bacteriuria (>100,000 Cfu/ml or >=100,000 Cfu/ml) Plus Pyuria (Any WBC) | 10 months | 13 participants |
Secondary
Bacteriuria With Multidrug-resistant Gram-negative Bacilli
All urine culture data will be reviewed to determine presence of multidrug-resistant gram-negative bacilli (resistance to ≥3 of the following antibiotics: ampicillinsulbactam,cefazolin, ceftriaxone, ceftazidime, fluoroquinolones, piperacillin-tazobactam, meropenem, imipenem, and trimethoprim-sulfamethoxazole).
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Cranberry Capsules | Bacteriuria With Multidrug-resistant Gram-negative Bacilli | 9 episodes |
| 2 Placebo Capsules | Bacteriuria With Multidrug-resistant Gram-negative Bacilli | 24 episodes |
Secondary
Number of Antibiotic Prescriptions
Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant.
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Cranberry Capsules | Number of Antibiotic Prescriptions | 1415 prescriptions |
| 2 Placebo Capsules | Number of Antibiotic Prescriptions | 1883 prescriptions |
Secondary
Number of Antibiotic Prescriptions for Suspected UTI
Chart review will be performed to determine the names and duration of antibiotic prescriptions prescribed by the primary provider on each participant's suspected UTI.
Time frame: One Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Cranberry Capsules | Number of Antibiotic Prescriptions for Suspected UTI | 692 prescriptions |
| 2 Placebo Capsules | Number of Antibiotic Prescriptions for Suspected UTI | 909 prescriptions |
Secondary
Number of Deaths
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Cranberry Capsules | Number of Deaths | 17 participants |
| 2 Placebo Capsules | Number of Deaths | 16 participants |
Secondary
Number of Episodes of Symptomatic UTI
Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met.
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Cranberry Capsules | Number of Episodes of Symptomatic UTI | 10 symptomatic urinary tract infections |
| 2 Placebo Capsules | Number of Episodes of Symptomatic UTI | 12 symptomatic urinary tract infections |
Secondary
Number of Hospitalizations
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Cranberry Capsules | Number of Hospitalizations | 33 hospitilizations |
| 2 Placebo Capsules | Number of Hospitalizations | 50 hospitilizations |
Secondary
Subjects With 1, 2, or 3 Episodes of UTIs
Suspected UTI episodes that are recorded in the medical record by the primary provider will be reviewed by chart review, symptoms will be recorded, and two adjudicators will determine if the definition of symptomatic UTI is met.
Time frame: One year
Population: There were 10 symptomatic UTIs in the treatment group (8 participants with 1 episode and 1 participant with 2 episodes) and 12 symptomatic UTIs in the control group (7 participants with 1 episode, 1 participant with 2 episodes, and 1 participant with 3 episodes).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2 Cranberry Capsules | Subjects With 1, 2, or 3 Episodes of UTIs | 1 episode | 8 participants |
| 2 Cranberry Capsules | Subjects With 1, 2, or 3 Episodes of UTIs | 2 episodes | 1 participants |
| 2 Cranberry Capsules | Subjects With 1, 2, or 3 Episodes of UTIs | 3 episodes | 0 participants |
| 2 Placebo Capsules | Subjects With 1, 2, or 3 Episodes of UTIs | 1 episode | 7 participants |
| 2 Placebo Capsules | Subjects With 1, 2, or 3 Episodes of UTIs | 2 episodes | 1 participants |
| 2 Placebo Capsules | Subjects With 1, 2, or 3 Episodes of UTIs | 3 episodes | 1 participants |
Other Pre-specified
Adherence to Capsule Intake by All Participants
measured by capsules removed from blister packs
Time frame: One year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2 Cranberry Capsules | Adherence to Capsule Intake by All Participants | 77.5 percentage of capsules |
| 2 Placebo Capsules | Adherence to Capsule Intake by All Participants | 82.6 percentage of capsules |
Other Pre-specified
Number of Adverse Events in Participants
Time frame: One year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2 Cranberry Capsules | Number of Adverse Events in Participants | Serious unrelated | 50 adverse events |
| 2 Cranberry Capsules | Number of Adverse Events in Participants | non-serious unrelated | 1731 adverse events |
| 2 Cranberry Capsules | Number of Adverse Events in Participants | non-serious related | 7 adverse events |
| 2 Placebo Capsules | Number of Adverse Events in Participants | Serious unrelated | 66 adverse events |
| 2 Placebo Capsules | Number of Adverse Events in Participants | non-serious unrelated | 1966 adverse events |
| 2 Placebo Capsules | Number of Adverse Events in Participants | non-serious related | 7 adverse events |