ProteinuriaPhase 3NCT00568178
An Extension Study Designed to Assess Effects of Losartan on Proteinuria in Pediatric Populations (MK-0954-326 AM1,EXT1(AM2))
A Phase 3 study testing Losartan Potassium and Comparator: amlodipine besylate in people with Proteinuria, run by Organon and Co.
Trial summary
The purpose of this study is to evaluate the effects of losartan on proteinuria in pediatric patients. Read more about this study
- Who is it for?
- Ages 12 months to 17 years
- Conditions the study is for
- Proteinuria
- What is being tested?
- Losartan Potassium and Comparator: amlodipine besylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 306 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2007to 1 Mar 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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)
About this study
Official title: 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.
Read the 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.
- Conditions
- Proteinuria
- Being tested
- Losartan Potassium, Comparator: Placebo (Losartan), Comparator: amlodipine besylate, Comparator: Placebo (amlodipine besylate), Placebo (Losartan)
- Medical subject headings
- Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losartan PotassiumDrug
Also called Cozaar®
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.
Comparator: Placebo (Losartan)Other
Placebo (losartan suspension), administered orally, once daily for 12 weeks
Comparator: amlodipine besylateDrug
Also called NORVASC®
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
Comparator: Placebo (amlodipine besylate)Other
Also called NORVASC®
Liquid suspension, 1mg/mL, titrated to 0.2 mg/kg/day (5 mg maximum dose) once daily, for 12 weeks
Placebo (Losartan)Other
Normotensive patients randomized to losartan placebo for 12 weeks.
Enalapril MaleateDrug
Also called Vasotec®, Renitec®
Enalapril 2.5-, 5-, 10-, and 20-mg tablets or enalapril suspension (1 mg/mL), oral administration, once daily for 36 months.
| Study group | Role | What they receive |
|---|---|---|
| Losartan Double-Blind Base Study (12-weeks) | Experimental | Normotensive participants received losartan.
Hypertensive participants received either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo). Receives: Drug: Losartan Potassium; Other: Comparator: Placebo (Losartan) |
| Amlodipine Double-Blind Base Study (12-weeks) | Active comparator | Hypertensive participants were randomized to receive either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo) for 12 weeks. Receives: Other: Comparator: Placebo (Losartan); Drug: Comparator: amlodipine besylate; Other: Comparator: Placebo (amlodipine besylate); Other: Placebo (Losartan) |
| Losartan Open-Label Extension Phase (Month 36) | Experimental | 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). Receives: Drug: Losartan Potassium |
| Enalapril Open-Label Extension Phase (Month 36) | Active comparator | 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). Receives: Drug: Enalapril Maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Double-Blind Treatment Phase: Percent Change From Baseline in Urinary Protein/Creatinine (Pr/Cr) Ratio (gm/gm) at 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.
Measured: Baseline and Week 12
Open Label Extension: Percent Change From Baseline of Urinary Pr/Cr Ratio (gm/gm) at 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.
Measured: Baseline and Month 36
Open Label Extension: Change From Baseline in Glomerular Filtration Rate (GFR) at 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.
Measured: Baseline and Month 36
Secondary outcomes (2)
Double-Blind Treatment Phase: Change From Baseline in Systolic Blood Pressure in Hypertensive Participants at Week 12
Measured: Baseline and Week 12
Double-Blind Treatment Phase: Change From Baseline in Diastolic Blood Pressure in Hypertensive Participants at Week 12
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2007 (estimated)
- Study start1 Jun 2007
- Primary completion1 Sep 2008
- Study completion1 Mar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ProteinuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 306 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00568178
- Sponsor's protocol ID
- 0954-326
- Other IDs
- 2006-006415-74
- Status last verified
- Feb 2022
- First submitted
- 3 Dec 2007
- Last updated
- 23 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, McCrary Sisk C, Lam C. Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome. Pediatr Nephrol. 2013 May;28(5):737-43. doi: 10.1007/s00467-012-2372-9. Epub 2012 Dec 4.
PubMed 23207876Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, Santoro EP, Sisk CM, Lam C. Losartan and enalapril are comparable in reducing proteinuria in children. Kidney Int. 2012 Oct;82(7):819-26. doi: 10.1038/ki.2012.210. Epub 2012 Jun 27.
PubMed 22739977Webb NJ, Lam C, Shahinfar S, Strehlau J, Wells TG, Gleim GW, Le Bailly De Tilleghem C. Efficacy and safety of losartan in children with Alport syndrome--results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial. Nephrol Dial Transplant. 2011 Aug;26(8):2521-6. doi: 10.1093/ndt/gfq797. Epub 2011 Feb 1.
PubMed 21285125
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Parallel, Placebo or Amlodipine-Controlled Study of the Effects of Losartan on Proteinuria in Pediatric Patients With or Without Hypertension
- ClinicalTrials.gov ID
- NCT00568178
- Acronym / sponsor ID
- 0954-326
- Conditions
- Proteinuria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 306 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2007 (actual)
- Primary completion
- 1 Sep 2008 (actual)
- Study completion
- 1 Mar 2011 (actual)
- First posted
- 5 Dec 2007 (estimated)
- Results
- Posted 30 Oct 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effects of losartan on proteinuria in pediatric patients.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Losartan Double-Blind Base Study (12-weeks) | Experimental | Drug: Losartan Potassium, Other: Comparator: Placebo (Losartan)Normotensive participants received losartan. Hypertensive participants received either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo). |
| Amlodipine Double-Blind Base Study (12-weeks) | Active comparator | Other: Comparator: Placebo (Losartan), Drug: Comparator: amlodipine besylate, Other: Comparator: Placebo (amlodipine besylate), Other: Placebo (Losartan)Hypertensive participants were randomized to receive either active losartan (plus amlodipine placebo) OR active amlodipine (plus losartan placebo) for 12 weeks. |
| Losartan Open-Label Extension Phase (Month 36) | Experimental | Drug: Losartan PotassiumParticipants 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). |
| Enalapril Open-Label Extension Phase (Month 36) | Active comparator | Drug: Enalapril MaleateParticipants 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). |
Who may qualify
- Ages
- 12 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Losartan PotassiumAlso: Cozaar®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. | Drug | Losartan Double-Blind Base Study (12-weeks), Losartan Open-Label Extension Phase (Month 36) |
| Comparator: Placebo (Losartan)Placebo (losartan suspension), administered orally, once daily for 12 weeks | Other | Amlodipine Double-Blind Base Study (12-weeks), Losartan Double-Blind Base Study (12-weeks) |
| Comparator: amlodipine besylateAlso: NORVASC®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 | Drug | Amlodipine Double-Blind Base Study (12-weeks) |
| Comparator: Placebo (amlodipine besylate)Also: NORVASC®Liquid suspension, 1mg/mL, titrated to 0.2 mg/kg/day (5 mg maximum dose) once daily, for 12 weeks | Other | Amlodipine Double-Blind Base Study (12-weeks) |
| Placebo (Losartan)Normotensive patients randomized to losartan placebo for 12 weeks. | Other | Amlodipine Double-Blind Base Study (12-weeks) |
| Enalapril MaleateAlso: Vasotec®, Renitec®Enalapril 2.5-, 5-, 10-, and 20-mg tablets or enalapril suspension (1 mg/mL), oral administration, once daily for 36 months. | Drug | Enalapril Open-Label Extension Phase (Month 36) |
Primary outcome
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.
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.
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.
2 secondary outcomes
Double-Blind Treatment Phase: Change From Baseline in Systolic Blood Pressure in Hypertensive Participants at Week 12
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23207876Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, McCrary Sisk C, Lam C. Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome. Pediatr Nephrol. 2013 May;28(5):737-43. doi: 10.1007/s00467-012-2372-9. Epub 2012 Dec 4.
- Derived from this study: PubMed 22739977Webb NJ, Shahinfar S, Wells TG, Massaad R, Gleim GW, Santoro EP, Sisk CM, Lam C. Losartan and enalapril are comparable in reducing proteinuria in children. Kidney Int. 2012 Oct;82(7):819-26. doi: 10.1038/ki.2012.210. Epub 2012 Jun 27.
- Derived from this study: PubMed 21285125Webb NJ, Lam C, Shahinfar S, Strehlau J, Wells TG, Gleim GW, Le Bailly De Tilleghem C. Efficacy and safety of losartan in children with Alport syndrome--results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial. Nephrol Dial Transplant. 2011 Aug;26(8):2521-6. doi: 10.1093/ndt/gfq797. Epub 2011 Feb 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Losartan Potassium and Comparator: amlodipine besylate in people with Proteinuria, run by Organon and Co.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00568178, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.