An Extension Study Designed to Assess Effects of Losartan on Proteinuria in Pediatric Populations (MK-0954-326 AM1,EXT1(AM2))

February 7, 2022 updated by: Organon and Co

A Randomized, Double-Blind, Parallel, Placebo or Amlodipine-Controlled Study of the Effects of Losartan on Proteinuria in Pediatric Patients With or Without Hypertension

The purpose of this study is to evaluate the effects of losartan on proteinuria in pediatric patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study included a 12-week double-blind treatment phase and a 36-month open-label extension phase. Participants who completed or discontinued the initial 12-week phase of the study and who opted to participate in the open label extension phase were randomized to either losartan or enalapril at a dose of the investigator's choosing for the duration of the extension. The open label extension was designed to continue until the 100th participant completed 3 years of follow-up.

Study Type

Interventional

Enrollment (Actual)

306

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participant is 1 to 17 years of age
  • Able to provide a first-morning urine sample each day during the study
  • Documented history of proteinuria associated with chronic kidney disease of any origin
  • Signed consent of parent and/or legal guardian

Exclusion Criteria:

  • Pregnant and/or nursing
  • Requires more than 2 medications to control high blood pressure
  • Has undergone major organ transplantation (e.g. heart, kidney, liver)
  • Known sensitivity to losartan or other similar drugs, or any history of angioneurotic edema
  • Known sensitivity to amlodipine or other calcium channel blocker
  • Requires cyclosporine to treat renal disease (kidney disease)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Losartan Double-Blind Base Study (12-weeks)

Normotensive participants received losartan.

Hypertensive participants received either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo).
Drug: Losartan Potassium

Losartan Use During the Double-Blind Treatment Phase:

Losartan potassium was administered orally as tablets; 25 or 50 milligrams (mg); or as a liquid suspension 2.5 mg/mL prepared for participants who weighed less than 25 kilograms (kg) or for those participants unable to swallow tablets. During the double-blind period, participants were initially randomized to either a once-daily weight-dependent dose of approximately 0.7 mg/kg (25 mg tablet; up to 50 mg per day) and at 2-weeks the dose was increased to a once-daily maximum weight-dependent dose of 1.4 mg/kg. The maximum dose of losartan, as specified in the protocol, was 50 mg/day (if the patient weighed <50 kg)

or 100 mg/day (if the patient weighed ≥50 kg).

Losartan Use During the Treatment Extension Phase:

Dose modifications of the drug were left up to the discretion of the Investigators based on each participant's level of tolerance.

Other Names:
  • Cozaar®
Other: Comparator: Placebo (Losartan)
Placebo (losartan suspension), administered orally, once daily for 12 weeks
Active Comparator: Amlodipine Double-Blind Base Study (12-weeks)
Hypertensive participants were randomized to receive either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo) for 12 weeks.
Other: Comparator: Placebo (Losartan)
Placebo (losartan suspension), administered orally, once daily for 12 weeks
Drug: Comparator: amlodipine besylate
Amlodipine besylate (1 mg/mL) liquid suspension, oral administration, titrated to 0.2 mg/kg/day (5 mg maximum dose) per day for 12 Weeks
Other Names:
  • NORVASC®
Other: Comparator: Placebo (amlodipine besylate)
Liquid suspension, 1mg/mL, titrated to 0.2 mg/kg/day (5 mg maximum dose) once daily, for 12 weeks
Other Names:
  • NORVASC®
Other: Placebo (Losartan)
Normotensive patients randomized to losartan placebo for 12 weeks.
Experimental: Losartan Open-Label Extension Phase (Month 36)
Participants were were carried over from the base study into the long-term safety extension. Participants in the extension were randomly assigned to either losartan or enalapril regardless of their previous randomized treatment. Dosing during the extension period (i.e. starting dose and any titration) was up to the investigator and varied by patient).
Drug: Losartan Potassium

Losartan Use During the Double-Blind Treatment Phase:

Losartan potassium was administered orally as tablets; 25 or 50 milligrams (mg); or as a liquid suspension 2.5 mg/mL prepared for participants who weighed less than 25 kilograms (kg) or for those participants unable to swallow tablets. During the double-blind period, participants were initially randomized to either a once-daily weight-dependent dose of approximately 0.7 mg/kg (25 mg tablet; up to 50 mg per day) and at 2-weeks the dose was increased to a once-daily maximum weight-dependent dose of 1.4 mg/kg. The maximum dose of losartan, as specified in the protocol, was 50 mg/day (if the patient weighed <50 kg)

or 100 mg/day (if the patient weighed ≥50 kg).

Losartan Use During the Treatment Extension Phase:

Dose modifications of the drug were left up to the discretion of the Investigators based on each participant's level of tolerance.

Other Names:
  • Cozaar®
Active Comparator: Enalapril Open-Label Extension Phase (Month 36)
Participants were were carried over from the base study into the long-term safety extension. Participants in the extension were randomly assigned to either losartan or enalapril regardless of their previous randomized treatment. Dosing during the extension period (i.e. starting dose and any titration) was up to the investigator and varied by patient).
Drug: Enalapril Maleate
Enalapril 2.5-, 5-, 10-, and 20-mg tablets or enalapril suspension (1 mg/mL), oral administration, once daily for 36 months.
Other Names:
  • Vasotec®
  • Renitec®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Double-Blind Treatment Phase: Percent Change From Baseline in Urinary Protein/Creatinine (Pr/Cr) Ratio (gm/gm) at Week 12
Time Frame: Baseline and Week 12

Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline*, after approximately twelve weeks of treatment.

Baseline is defined as values obtained at Visit 3, Week (-1) during the Single Blind Run-in period.
Baseline and Week 12
Open Label Extension: Percent Change From Baseline of Urinary Pr/Cr Ratio (gm/gm) at Month 36
Time Frame: Baseline and Month 36

Change in urinary protein excretion, determined as urinary Pr/Cr ratio compared to baseline*, after approximately three years of treatment.

*The baseline for efficacy data in the extension was defined as the last value obtained in the double-blind treatment phase.
Baseline and Month 36
Open Label Extension: Change From Baseline in Glomerular Filtration Rate (GFR) at Month 36
Time Frame: Baseline and Month 36

The outcome measure of glomerular filtration rate was based on mL/min/1.73m^2, as determined by the Schwartz formula:

GFR = _____0.55 x height (cm)_______ divided by serum creatinine (mg/dL)

GFR values were compared to the baseline GFR measure.

[Note: For male participants, ages 13 to 17 years, 0.70 was used as

the multiplier in place of 0.55]

Baseline in regard to the extension is defined as the last value obtained in the double-blind treatment phase.
Baseline and Month 36

Secondary Outcome Measures

Outcome Measure
Time Frame
Double-Blind Treatment Phase: Change From Baseline in Systolic Blood Pressure in Hypertensive Participants at Week 12
Time Frame: Baseline and Week 12
Baseline and Week 12
Double-Blind Treatment Phase: Change From Baseline in Diastolic Blood Pressure in Hypertensive Participants at Week 12
Time Frame: Baseline and Week 12
Baseline and Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Organon and Co

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2007

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

December 3, 2007

First Submitted That Met QC Criteria

December 3, 2007

First Posted (Estimate)

December 5, 2007

Study Record Updates

Last Update Posted (Actual)

February 9, 2022

Last Update Submitted That Met QC Criteria

February 7, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0954-326
  • 2006-006415-74 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Proteinuria

Clinical Trials on Losartan Potassium

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Algeria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe