E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lower Uncomplicated Urinary Tract Infection |
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E.1.1.1 | Medical condition in easily understood language |
Lower Uncomplicated Urinary Tract Infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024981 |
E.1.2 | Term | Lower urinary tract infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Identify and compare the efficacy of pivmecillinam 400 mg t.i.d in a 3-day respectively 5-day regimen, against community acquired lower urinary tract infections i.e. in women at the age of 18-70 years old. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Women in the age of 18-70 years old, with clinical features of community acquired uncomplicated UTI and ability to understand the study and give written consent. Patients should have a symptom cumulative score of ≥ 2 p (i.e. none, mild, moderate or severe, scoring 0-3, respectively) in accordance to the validated questionnaires for uncomplicated UTI. The following signs and symptoms are included: • Dysuria (i.e. pain or burning sensation on urination) • Urgency (i.e. feeling an increased and more frequent need to urinate) • Pollakisuria/frequency (i.e. urinating more frequently than usually) An accepted definition of uncomplicated urinary tract infections is symptoms in concordance with uUTI and significant bacteriuria of uropathogenic bacteria1, but we have chosen not include the latter criteria in our ITT analysis. This is because we want the included patients in the ITT group to mimic the realistic settings as much as possible (i.e. in which patients with uUTI will receive antibiotic therapy without urine samples in most primary care settings).
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E.4 | Principal exclusion criteria |
Absolute exclusion criteria are:
• Clear signs of pyelonephritis (high fever ≥38,5°C or back/flank pain), or high suspicion of pyelonephritis • Allergy to penicillins Symptom related exclusion criteria: • Clear vaginal symptoms, i.e. discharge and/or pain Any condition that may lead or predispose to complicated urinary infection: • Indwelling urinary catheter • Pregnancy • Immunosuppressive therapy • Abnormal/pathological urinary tracts (e.g. renal disease, known presence of urinary stones, past urinary interventions/surgery, genetic aciduria) • Hard treated recurrent UTIs • Serious neurological disease affecting the bladder (i.e. paraplegia, multiple sclerosis, epilepsy) Other complicating or contradictive conditions: • Ongoing breastfeeding • Ongoing/current antibiotic therapy • Oesophageal stricture • Current intake of allopurinol (i.e. increases the risk of allergic skin reaction to mecillinam) or probenecid (i.e. decrease the renal excretion of mecillinam) • Currently part of another clinical trail • Unwilling to participate in study (i.e. not wanting to sign consent form) • Inability/unable to understand and/or take part in the clinical trial • Incapable of following the instructions of the study There are no known drugs beside those listed in the exclusion criteria to have significant interaction with mecillinam. Thus, all other drugs (prescribed or non-prescription) should be taken as usual throughout the study (which will be explained by the GP). However, all drugs should be registered in the diary and/or given permission by the patient for us to look it up on the national database of medicine prescriptions. |
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E.5 End points |
E.5.1 | Primary end point(s) |
We have 2 co-primary endpoints Co-primary endpoint no. 1 – initial clinical cure (i.e. what group experience clinical cure fastest). Co-primary endpoint no. 2 – initial bacteriological cure rate (i.e. control urine sample no. 1 compared to pre-treatment urine sample).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Both primary endpoints will be evaluated at the intervene analysis (i.e. the first 300 included patients to see if there is a large difference that will make it unethical for us to proceed with the study), and finally at the end of the trail (i.e. after the last patient is included |
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E.5.2 | Secondary end point(s) |
1. Clinical signs and symptoms in uncomplicated urinary tract infections in women. 2. Frequency and timing of relapse of symptoms and/or bacteriuria. 3. Bacteriological findings (i.e. ESBL producing bacteria) 4. Complications (i.e. urosepsis and/or pyelonephritis)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints will be evaluated at the intervene analysis (i.e. the first 300 included patients to see if there is a large difference that will make it unethical for us to proceed with the study), and finally at the end of the trail (i.e. after the last patient is included |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |