Clinical Trial Result Information

Protocol number
ML18113

Title of Study
An open-label, randomized, multicenter study to assess diuresis and safety of torasemide versus furosemide in the treatment of patients with acute/chronic renal failure or nephrotic syndrome.

Sponsor
Shanghai Roche Pharmaceutical Ltd.

Company division
Pharmaceutical

Product name
Torem

Generic name
torasemide

Therapeutic area
Renal Failure

Clinical study summary
This was a randomized, open-label study in patients with renal failure or nephrotic syndrome, to investigate the efficacy and safety of Torem (torasemide) compared to that of furosemide.

Study center(s)
6 centers in China.

Phase of development
III

Objectives
Primary: To compare the diuretic effect and safety of Torem and furosemide in the treatment of patients with acute/chronic renal failure or nephrotic syndrome.
Secondary: To compare the electrolyte, acid-base and water balance and blood pressure normalization in patients with acute/chronic renal failure or nephrotic syndrome during treatment with Torem and furosemide.

Methodology
Patients were randomly assigned to either the Torem or furosemide group. During the initial 7 days, the dose was up-titrated in order to obtain effectual diuresis. The initial dose (day 1 and day 2) was 20 mg/40 mg (TOR/FUR) i.v. If effectual diuresis was not reached the dose was up-titrated by 40 mg/80 mg each day up to the 7th day on which the ceiling dose of 200 mg/400 mg was to be reached.
Once the individual maintenance dose was determined (presence of effectual diuresis), it was given for an additional day to complete the study treatment.

Number of patients (planned/analyzed)
Planned: 120; 182 enrolled.

Diagnosis and main criteria for inclusion
Patients aged 18 to 70 years old with a diagnosis of acute/chronic renal failure or nephrotic syndrome.

Test product, dose and mode of administration or test procedure
Torem (torasemide) 20 mg iv daily up-titrated to a maximum of 200 mg iv.

Duration of treatment
3 – 8 days.

Reference therapy, dose and mode of administration or reference procedure
Furosemide 40 mg iv daily up-titrated to a maximum of 400 mg iv.

Criteria for evaluation (efficacy, safety)
Primary efficacy parameter: Effectual diuresis rate in both treatment groups.
Secondary efficacy parameter: Mean time to effectual diuresis, mean dosage on effectual diuresis, change in body weight pre-and post treatment, change in status of edema pre- and post treatment.
Safety parameters: Adverse events, changes of serum electrolytes.

Statistical methods
Descriptive statistics were used for all the efficacy, safety and demographic variables, including the primary variable.

Summary (efficacy, safety, other results)
Efficacy: A total of 91 out of 95 patients in the Torem group, and 85 out of 87 patients in the furosemide group, achieved effectual diuresis. Due to a company decision not to develop Torem in renal failure full analysis of the efficacy parameters was not undertaken.
Safety: A total of 25 AEs in the Torem arm, and 31 AEs in the furosemide arm, were reported during the study. A higher percentage of AEs were considered related to furosemide treatment (58%) than to Torem treatment (36%). One patient in the furosemide group died of cerebral infarction, considered possibly related to treatment. There were no SAEs in the Torem group.

Conclusions
Due to the decision not to pursue a further indication for Torem, a full analysis of this study was not conducted, and no conclusions can therefore be drawn.

Date of report
5/1/2006

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