Non‑inferiority of a 7‑day versus 14‑day oral ciprofloxacin regimen for male urinary tract infection with systemic involvement: a randomized controlled trial

The primary objective is to determine whether a short‑course ciprofloxacin strategy (≥4 days of ciprofloxacin, total 7 days) is non‑inferior to a 14‑day regimen in achieving clinical cure in men with urinary tract infection with systemic involvement.

The trial enrolled adult male participants with Urinary tract infection with systemic involvement. Eligible individuals were required to be 18 years or older, haemodynamically stable, and to have a monobacterial infection caused by a ciprofloxacin‑sensitive uropathogen. Selection was based on clinical presentation meeting the diagnostic criteria for systemic involvement (fever ≥38 °C, flank pain, hypotension, elevated inflammatory markers, or bacteraemia) and on confirmation of susceptibility. Participants were required to be receiving empiric antibiotic therapy approved in the protocol. General health status was limited to patients without sepsis or septic shock (sepsis‑3 criteria). Lifestyle factors such as diet, physical activity, or habits were not stipulated as eligibility requirements. The sponsor did not provide information on the total number of participants enrolled.

The study is a multicenter, randomized, double‑blind, placebo‑controlled, parallel‑group trial designed to assess the non‑inferiority of a 7‑day ciprofloxacin regimen compared with a 14‑day regimen in adult males with urinary tract infection with systemic involvement. Eligible participants are screened, consented, and randomized on the same day to receive either ciprofloxacin 500 mg tablets (total daily dose 1500 mg) plus matching placebo or ciprofloxacin 500 mg tablets for the full 14 days, with placebo tablets administered during days 8‑14 in the short‑course arm to maintain blinding. The overall participant involvement lasts approximately six to eight weeks, encompassing a screening visit, baseline/randomization visit, treatment period, and follow‑up assessments. Study visits are scheduled as follows:

• Screening visit: verification of inclusion criteria, assessment of haemodynamic stability, collection of baseline laboratory values and urine culture.
• Baseline/randomization visit (day 0): allocation to treatment arm, dispensing of study medication, and documentation of initial clinical status.
• End‑of‑treatment visit (day 7 for the short‑course arm or day 14 for the standard arm): evaluation of adherence, collection of safety data, and assessment of interim clinical response.
• Follow‑up visit 14 days after completion of therapy: primary endpoint assessment of clinical cure (resolution of systemic signs/symptoms and no need for additional antibiotics).
• Follow‑up visit 28 days after completion of therapy: evaluation of secondary endpoints including early and late UTI relapse, recurrence, mortality, adverse drug reactions, and hospital readmission.
• End‑of‑study visit (day 28 post‑treatment): final safety and efficacy assessments.

The investigational product is ciprofloxacin 500 mg film‑coated tablets (Ciprofloxacine EG 500 mg). The medication is administered orally at a total daily dose of 1500 mg, typically divided into three tablets taken once daily. The formulation is a film‑coated tablet intended for systemic absorption.

The comparator is a placebo consisting of microcrystalline cellulose identical in appearance to the over‑encapsulated ciprofloxacin 500 mg tablets. The placebo is presented in an HPMC capsule (Vcaps plus, size 000) with a Swedish orange coloration and contains no active pharmaceutical ingredient.

Participants are randomized to receive either a short‑course regimen of ciprofloxacin for at least 4 days followed by placebo to complete a 7‑day treatment period, or a continuous 14‑day course of ciprofloxacin. Dosing is performed once daily according to the assigned schedule.

The primary efficacy parameter is the clinical cure rate, defined as resolution of systemic signs and symptoms to the pre‑admission state without the need for additional antibiotic therapy. This outcome is evaluated 14 days after the completion of the assigned antibiotic regimen.

Secondary efficacy assessments include:

• Early UTI relapse (new infection with the same uropathogen) – assessed 14 days post‑treatment.
• Late UTI relapse (same uropathogen) – assessed 28 days post‑treatment.
• Early UTI recurrence (new infection with a different uropathogen) – assessed 14 days post‑treatment.
• Late UTI recurrence (different uropathogen) – assessed 28 days post‑treatment.
• UTI‑related mortality – assessed 28 days post‑treatment.
• Investigational medical product‑related adverse drug reactions – assessed 14 days post‑treatment.
• UTI‑related hospital readmission – assessed 28 days post‑treatment.