Prostatitis
Conditions
Keywords
Chronic Prostatitis, Prostatitis, levofloxacin, Levaquin
Brief summary
The purpose of this study is to compare the safety and effectiveness of levofloxacin 750 mg for 2 weeks or 750 mg for 3 weeks, compared to levofloxacin 500 mg for 4 weeks in the treatment of chronic prostatitis.
Detailed description
The optimal duration of treatment for chronic prostatitis remains unclear. Historically, therapy for chronic prostatitis with other classes of antibacterials resulted in poor outcomes and prolonged time taking the medication. Levofloxacin belongs to the quinolone class of antibacterials and has been used to treat chronic prostatitis with 500mg of levofloxacin taken orally once a day for 4 weeks. This multicenter, double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), randomized (patients are assigned different treatments based on chance) study is designed to see if giving levofloxacin at a higher dose for shorter periods of time is safe and effective in treating chronic prostatitis. Safety analyses will involve the examination of the incidence, severity, and type of adverse events and changes in physical findings including vital signs and clinical laboratory tests. Patients will receive one of the following three dosing options: levofloxacin 750 mg orally administered once-a-day for 2 weeks followed by placebo once-a-day for two weeks for a total of 4 weeks, or levofloxacin 750 mg orally once-a-day for 3 weeks followed by placebo once-a-day for one week for a total of 4 weeks, or levofloxacin 500 mg orally once-a-day for 4 weeks.
Interventions
DRUGlevofloxacin
750mg tablet once daily for 2 weeks followed by 2 weeks of placebo.
Sponsors
PriCara, Unit of Ortho-McNeil, Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males 40 years of age or older * A clinical diagnosis of chronic prostatitis as evidenced by the following two criteria: 1. Clinical signs and symptoms of prostatitis including a soft, tender prostate without noticeable nodularity with one or more of the following signs or symptoms: painful or difficult urination, suprapubic discomfort, painful ejaculation, low back pain, perineal discomfort, urinary frequency, urinary urgency or hesitancy, decreased urinary stream, urinary retention, pain on digital rectal examination, perineal tenderness or pain, fever, chills. 2. A history of chronic prostatitis as defined as: symptomatic prostatitis - a clinical diagnosis of prostatitis having been made for at least one previous episode that lasted four weeks, or two or more episodes during the previous twelve months.
Exclusion criteria
* Any condition which may interfere with the evaluation of study drug including transurethral prostatectomy within six months of enrollment, the presence of a permanent transurethral catheter or a history of cystostomy or nephrostomy * Taking hormone therapy * Known prostatic carcinoma * Allergy to levofloxacin, ofloxacin, ciprofloxacin, or other members of the quinolone class of antibacterials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Success | Posttherapy Visit (Study Day 33-36) | Defined as cured or improved. Response is based on the resolution of signs and symptoms at post-therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Relief (Resolved) | Posttherapy Visit (Study Day 33-36) | Participants With Resolution of Prostatitis Signs and Symptoms; Resolution is defined as symptoms present (mild, moderate or severe) at Screening/Admission and absent (none) at the Posttherapy evaluation. |
| Clinical Success (Non-Relapse) or Failure (Relapse) | Poststudy Telephone contact at 6 weeks | Number of Clinical Successes or Failures at the 6-Week Poststudy Telephone Contact for Participants Cured/Improved at the Posttherapy Visit |
| Total NIH-CPSI Score | Screening/Admission, On-Therapy, Week 3, Week 4, Posttherapy (Study Day 33-36) | National Institute of Health-Chronic Prostatitis Symptom Index numerically rates a total score (0-43) where 0 indicates no symptoms across any of the domains (pain or discomfort, urination, quality of life). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levofloxacin 750mg for 2 Weeks levofloxacin, 750mg tablet once daily for 2 weeks followed by 2 weeks of placebo. | 81 |
| Levofloxacin 750mg for 3 Weeks levofloxacin, 750mg tablet once daily for 3 weeks followed by 1 week of placebo. | 81 |
| Levofloxacin 500mg for 4 Weeks levofloxacin, 500mg tablet once daily for 4 weeks. | 80 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 9 | 3 |
| Overall Study | Culture Show Fluoroquinolone Resistance | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 4 | 4 | 5 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 |
| Overall Study | Patient Left Town and Forgot Medication | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | Urine Cult. Yield Resistant to Levaquin | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | Levofloxacin 750mg for 2 Weeks | Levofloxacin 750mg for 3 Weeks | Levofloxacin 500mg for 4 Weeks | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 10 Participants | 15 Participants | 41 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 71 Participants | 65 Participants | 201 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 81 Participants | 81 Participants | 80 Participants | 242 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 43 / — | 42 / — | 38 / — |
| serious Total, serious adverse events | 2 / — | 1 / — | 0 / — |
Outcome results
Primary
Clinical Success
Defined as cured or improved. Response is based on the resolution of signs and symptoms at post-therapy.
Time frame: Posttherapy Visit (Study Day 33-36)
Population: Modified Intent to Treat (mITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levofloxacin 750mg for 2 Weeks | Clinical Success | 46 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success | 48 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success | 52 Participants |
95% CI: [-0.089, 0.215]
95% CI: [-0.106, 0.195]
Secondary
Clinical Success (Non-Relapse) or Failure (Relapse)
Number of Clinical Successes or Failures at the 6-Week Poststudy Telephone Contact for Participants Cured/Improved at the Posttherapy Visit
Time frame: Poststudy Telephone contact at 6 weeks
Population: Modified Intent-to-Treat Population (mITT) (Participants Cured/Improved at the Posttherapy Visit)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 0 participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 38 participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 5 participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 3 participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 1 participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 12 participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 32 participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 3 participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 5 participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 44 participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 2 participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 1 participants |
Secondary
Clinical Success (Non-Relapse) or Failure (Relapse)
Number of Clinical Successes or Failures at 3 Month Poststudy Telephone Contact for Participants Cured/Improved at the Posttherapy Visit
Time frame: Poststudy Telephone contact at 3 Months
Population: Modified Intent to Treat (mITT) (Participants Cured/Improved at the Posttherapy Visit)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 8 Participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 30 Participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 0 Participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 8 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 17 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 24 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 6 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 1 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 9 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 1 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 38 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 4 Participants |
Secondary
Clinical Success (Non-Relapse) or Failure (Relapse)
Number of Clinical Successes or Failures at the 6-month Poststudy Telephone Contact For Participants Cured/Improved at the Posttherapy Visit
Time frame: Poststudy Telephone Contact at 6 Months
Population: Modified Intent to Treat (mITT) (Participants Cured/Improved at the Posttherapy Visit)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 10 Participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 19 Participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 1 Participants |
| Levofloxacin 750mg for 2 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 16 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 24 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 19 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 4 Participants |
| Levofloxacin 750mg for 3 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 1 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Unable to Evaluate | 1 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Failure | 6 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Clinical Success | 31 Participants |
| Levofloxacin 500mg for 4 Weeks | Clinical Success (Non-Relapse) or Failure (Relapse) | Missing | 14 Participants |
Secondary
Symptom Relief (Resolved)
Participants With Resolution of Prostatitis Signs and Symptoms; Resolution is defined as symptoms present (mild, moderate or severe) at Screening/Admission and absent (none) at the Posttherapy evaluation.
Time frame: Posttherapy Visit (Study Day 33-36)
Population: Modified Intent to Treat (mITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Other (n=5, 8, 8) | 1 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Decreased urinary stream (n=50, 47, 52) | 24 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Painful ejaculation (n=32, 39, 34) | 17 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Perineal tenderness or pain (n=44, 38, 43) | 28 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Dysuria (n=35, 43, 42) | 23 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Low back pain (n=43, 44, 44) | 20 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Hesitancy (n=37, 39, 54) | 19 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Frequency (n=58, 63, 62) | 29 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Perineal discomfort (n=40, 42, 50) | 20 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Urgency (n=48, 52, 58) | 20 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Fever (n=3, 2, 1) | 2 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Pain on digital rectal examination (n=60, 59, 61) | 30 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Chills (n=4, 5, 7) | 3 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Urinary retention (n=24, 26, 27) | 13 Participants |
| Levofloxacin 750mg for 2 Weeks | Symptom Relief (Resolved) | Suprapubic discomfort (n=41, 36, 45) | 24 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Hesitancy (n=37, 39, 54) | 16 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Frequency (n=58, 63, 62) | 24 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Perineal tenderness or pain (n=44, 38, 43) | 24 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Chills (n=4, 5, 7) | 3 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Urgency (n=48, 52, 58) | 28 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Dysuria (n=35, 43, 42) | 29 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Suprapubic discomfort (n=41, 36, 45) | 19 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Painful ejaculation (n=32, 39, 34) | 23 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Low back pain (n=43, 44, 44) | 22 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Perineal discomfort (n=40, 42, 50) | 19 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Decreased urinary stream (n=50, 47, 52) | 21 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Urinary retention (n=24, 26, 27) | 13 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Pain on digital rectal examination (n=60, 59, 61) | 30 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Other (n=5, 8, 8) | 5 Participants |
| Levofloxacin 750mg for 3 Weeks | Symptom Relief (Resolved) | Fever (n=3, 2, 1) | 2 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Fever (n=3, 2, 1) | 1 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Decreased urinary stream (n=50, 47, 52) | 30 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Dysuria (n=35, 43, 42) | 27 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Other (n=5, 8, 8) | 5 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Urinary retention (n=24, 26, 27) | 17 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Urgency (n=48, 52, 58) | 35 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Frequency (n=58, 63, 62) | 30 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Chills (n=4, 5, 7) | 7 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Perineal tenderness or pain (n=44, 38, 43) | 28 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Pain on digital rectal examination (n=60, 59, 61) | 42 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Perineal discomfort (n=40, 42, 50) | 29 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Low back pain (n=43, 44, 44) | 26 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Painful ejaculation (n=32, 39, 34) | 20 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Hesitancy (n=37, 39, 54) | 38 Participants |
| Levofloxacin 500mg for 4 Weeks | Symptom Relief (Resolved) | Suprapubic discomfort (n=41, 36, 45) | 30 Participants |
Secondary
Total NIH-CPSI Score
National Institute of Health-Chronic Prostatitis Symptom Index numerically rates a total score (0-43) where 0 indicates no symptoms across any of the domains (pain or discomfort, urination, quality of life).
Time frame: Screening/Admission, On-Therapy, Week 3, Week 4, Posttherapy (Study Day 33-36)
Population: Modified Intent to Treat (mITT)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Levofloxacin 750mg for 2 Weeks | Total NIH-CPSI Score | Week 4 (Visit 3) (n=53, 57, 61) | 5.1 Score on a scale |
| Levofloxacin 750mg for 2 Weeks | Total NIH-CPSI Score | On-Therapy (n=70, 70, 73) | 7.2 Score on a scale |
| Levofloxacin 750mg for 2 Weeks | Total NIH-CPSI Score | Screening/Admission (n=73, 74, 75) | 11.8 Score on a scale |
| Levofloxacin 750mg for 2 Weeks | Total NIH-CPSI Score | Posttherapy (Visit 4) (n=70, 71, 71) | 5.4 Score on a scale |
| Levofloxacin 750mg for 2 Weeks | Total NIH-CPSI Score | Week 3 (Visit 2) (n=62, 65, 68) | 6.5 Score on a scale |
| Levofloxacin 750mg for 3 Weeks | Total NIH-CPSI Score | On-Therapy (n=70, 70, 73) | 6.6 Score on a scale |
| Levofloxacin 750mg for 3 Weeks | Total NIH-CPSI Score | Week 3 (Visit 2) (n=62, 65, 68) | 6.5 Score on a scale |
| Levofloxacin 750mg for 3 Weeks | Total NIH-CPSI Score | Screening/Admission (n=73, 74, 75) | 12.0 Score on a scale |
| Levofloxacin 750mg for 3 Weeks | Total NIH-CPSI Score | Week 4 (Visit 3) (n=53, 57, 61) | 4.9 Score on a scale |
| Levofloxacin 750mg for 3 Weeks | Total NIH-CPSI Score | Posttherapy (Visit 4) (n=70, 71, 71) | 5.0 Score on a scale |
| Levofloxacin 500mg for 4 Weeks | Total NIH-CPSI Score | Posttherapy (Visit 4) (n=70, 71, 71) | 4.6 Score on a scale |
| Levofloxacin 500mg for 4 Weeks | Total NIH-CPSI Score | Week 4 (Visit 3) (n=53, 57, 61) | 4.5 Score on a scale |
| Levofloxacin 500mg for 4 Weeks | Total NIH-CPSI Score | Week 3 (Visit 2) (n=62, 65, 68) | 5.6 Score on a scale |
| Levofloxacin 500mg for 4 Weeks | Total NIH-CPSI Score | On-Therapy (n=70, 70, 73) | 6.9 Score on a scale |
| Levofloxacin 500mg for 4 Weeks | Total NIH-CPSI Score | Screening/Admission (n=73, 74, 75) | 12.9 Score on a scale |