Renal Insufficiency, ChronicPhase 3NCT01485978
Efficacy and Safety Study to Delay Renal Failure in Children With Alport Syndrome
A Phase 3 study testing Ramipril in people with Renal Insufficiency, Chronic, run by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH at 1 site in Germany.
Trial summary
This is a phase III, multi-centre, randomised, placebo-controlled, patient and investigator-blind study in paediatric patients with early stages of Alport syndrome to assess the safety and efficacy of the ACEi ramipril in slowing disease progression. Read more about this study
- Who is it for?
- Ages 24 months to 18 years
- Conditions the study is for
- Renal Insufficiency, Chronic
- What is being tested?
- Ramipril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2012to Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 24 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Definitive diagnosis of Alport syndrome: Kidney biopsy (patient or affected relative/s), and/or mutation analysis (hemizygous X-chromosomal or homozygous autosomal-recessive) and assessment of criteria for clinical diagnosis (haematuria, positive family history regarding kidney diseases, ocular changes, labyrinthine hearing loss)
- Alport syndrome levels 0, I or II at screening (microhaematuria without microalbuminuria or microalbuminuria [30-300 mg albumin/gCrea]) or proteinuria >300 mg albumin/gCrea with GFR>80ml/min). Patients with Alport stage II are not subject to randomization but are treated opel label.
- Aged between ≥24 months and <18 years at screening
- Assent from patient and informed consent from parents/legal guardian
Who cannot join
- Uncertain diagnosis or variants of Alport syndrome such as a heterozygous carrier
- Alport syndrome levels III, or IV (albuminuria >300 mg/g Crea, creatinine clearance <60 mL/min, or end stage renal failure [ESRF])
- Known allergies or intolerances to ramipril or related compounds
- Known contraindication for ACEi-therapy
- Additional chronic renal, pulmonary or cardiac diseases
- Pregnancy and lactation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Prospective Therapy Trial to Delay Renal Failure in Children With Alport Syndrome
This is a phase III, multi-centre, randomised, placebo-controlled, patient and investigator-blind study in paediatric patients with early stages of Alport syndrome to assess the safety and efficacy of the ACEi ramipril in slowing disease progression.
Alport syndrome stages that describe the extent of renal damage and loss of function are defined as:
Read more
- 0 Microhaematuria without microalbuminuria (usually at birth)
- I Microalbuminuria (30-300 mg albumin/gCrea)
- II Proteinuria >300 mg albumin/gCrea
- III > 25% decline of normal renal function (creatinine clearance)
- IV End stage renal failure (ESRF)
Eligible patients with Alport stages 0 and I will be randomly assigned at a 2:1 ratio to receive once daily ramipril or placebo. In addition, Alport stage II patients may be treated open Label. Eligible patients who, or whose parents/legal guardian refuse randomisation after eligibility is confirmed, and patients who have been treated with ramipril prior to the study, may be treated open-label with ramipril as per protocol. The total number of patients will not exceed 120, with the number of randomised patients not exceeding 60, and the number of patients treated open label from Day 1 of the study aimed to be approximately 60.
Randomised patients whose disease progresses to the next disease level during the 3 year treatment period will be unblinded, and open label ramipril treatment will be initiated and continued, respectively, depending on prior treatment randomisation.
- Conditions
- Renal Insufficiency, Chronic
- Being tested
- Ramipril, placebo to ramipril
- Keywords
- Alport Syndrome, chronic kidney disease, renal fibrosis, nephroprotection, pediatric study
- Medical subject headings
- Renal Insufficiency, Chronic, Nephritis, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamiprilDrug
Ramipril (Delix) tablets containing 2.5 mg ramipril, oral application with 1 to 6 mg per body surface area ramipril once daily for 3 years.
placebo to ramiprilDrug
Oral application of placebo to ramipril, once daily with 1 to 6 mg per body surface area for 3 years or until disease progression.
RamiprilDrug
Oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years as per protocol.
| Study group | Role | What they receive |
|---|---|---|
| Ramipril blinded | Active comparator | oral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years Receives: Drug: Ramipril |
| placebo to ramipril | Placebo comparator | Oral placebo treatment to ramipril once daily for 3 years or until progress to next disease level. After progression to next disease level, patients will be unblinded, and ramipril treatment will be initiated. Receives: Drug: placebo to ramipril |
| open label ramipril | Other | Open label treatment with ramipril as per protocol, if randomization is refused. Receives: Drug: Ramipril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to next disease level
Time to progression of Alport Syndrome to the next disease level within 3 years under ramipril treatment compared to placebo, for all randomised patients.
Measured: within 3 years
Incidence of Adverse Drug Events before progression
Incidence of adverse drug events (ADEs, e.g., angioedema, acute renal failure, hyperkalaemia) under ramipril treatment before disease progression compared to placebo before disease progression, for all randomised patients.
Measured: within 3 years
Secondary outcomes (2)
Albuminuria after three years
Albuminuria after 3 years corrected for baseline albuminuria for patients randomised to receive ramipril compared to placebo.
Measured: after 3 years
Adverse Drug Events over three years
Incidence of ADEs (e.g., angioedema, acute renal failure, hyperkalaemia) during 3 years of treatment for patients randomised to receive ramipril compared to placebo.
Measured: after 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2011 (estimated)
- Study startMar 2012
- Primary completionSep 2018
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Renal Insufficiency, ChronicStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Goettingen, German Federal Ministry of Education and Research
- Responsible party
- Sponsor
- Investigators
- Oliver Gross, Prof., Study chair, University Medical Center Goettingen, Department Nephrology and Rheumatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01485978
- Sponsor's protocol ID
- EARLY_PRO-TECT_ALPORT
- Status last verified
- Jun 2020
- First submitted
- 2 Dec 2011
- Last updated
- 17 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gross O, Tonshoff B, Weber LT, Pape L, Latta K, Fehrenbach H, Lange-Sperandio B, Zappel H, Hoyer P, Staude H, Konig S, John U, Gellermann J, Hoppe B, Galiano M, Hoecker B, Ehren R, Lerch C, Kashtan CE, Harden M, Boeckhaus J, Friede T; German Pediatric Nephrology (GPN) Study Group and EARLY PRO-TECT Alport Investigators. A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome. Kidney Int. 2020 Jun;97(6):1275-1286. doi: 10.1016/j.kint.2019.12.015. Epub 2020 Jan 17.
PubMed 32299679Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021 Mar;36(3):711-719. doi: 10.1007/s00467-020-04819-6. Epub 2020 Nov 6.
PubMed 33159213Boeckhaus J, Hoefele J, Riedhammer KM, Tonshoff B, Ehren R, Pape L, Latta K, Fehrenbach H, Lange-Sperandio B, Kettwig M, Hoyer P, Staude H, Konrad M, John U, Gellermann J, Hoppe B, Galiano M, Gessner M, Pohl M, Bergmann C, Friede T, Gross O; GPN Study Group and EARLY PRO-TECT Alport Investigators. Precise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial. Clin Genet. 2021 Jan;99(1):143-156. doi: 10.1111/cge.13861. Epub 2020 Oct 25.
PubMed 33040356Ahmed R, Duerr U, Gavenis K, Hilgers R, Gross O. Challenges for academic investigator-initiated pediatric trials for rare diseases. Clin Ther. 2014 Feb 1;36(2):184-90. doi: 10.1016/j.clinthera.2014.01.013.
PubMed 24529291
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Prospective Therapy Trial to Delay Renal Failure in Children With Alport Syndrome
- ClinicalTrials.gov ID
- NCT01485978
- Acronym / sponsor ID
- EARLY_PRO-TECT_ALPORT
- Conditions
- Renal Insufficiency, Chronic
- Keywords
- Alport Syndrome, chronic kidney disease, renal fibrosis, nephroprotection, pediatric study
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Institut fuer anwendungsorientierte Forschung und klinische Studien GmbHUniversity, hospital or other
- Collaborators
- University Medical Center Goettingen, German Federal Ministry of Education and Research
- Study start
- Mar 2012
- Primary completion
- Sep 2018 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 6 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase III, multi-centre, randomised, placebo-controlled, patient and investigator-blind study in paediatric patients with early stages of Alport syndrome to assess the safety and efficacy of the ACEi ramipril in slowing disease progression.
Alport syndrome stages that describe the extent of renal damage and loss of function are defined as:
- 0 Microhaematuria without microalbuminuria (usually at birth)
- I Microalbuminuria (30-300 mg albumin/gCrea)
- II Proteinuria >300 mg albumin/gCrea
- III > 25% decline of normal renal function (creatinine clearance)
- IV End stage renal failure (ESRF)
Eligible patients with Alport stages 0 and I will be randomly assigned at a 2:1 ratio to receive once daily ramipril or placebo. In addition, Alport stage II patients may be treated open Label. Eligible patients who, or whose parents/legal guardian refuse randomisation after eligibility is confirmed, and patients who have been treated with ramipril prior to the study, may be treated open-label with ramipril as per protocol. The total number of patients will not exceed 120, with the number of randomised patients not exceeding 60, and the number of patients treated open label from Day 1 of the study aimed to be approximately 60.
Randomised patients whose disease progresses to the next disease level during the 3 year treatment period will be unblinded, and open label ramipril treatment will be initiated and continued, respectively, depending on prior treatment randomisation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ramipril blinded | Active comparator | Drug: Ramipriloral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years |
| placebo to ramipril | Placebo comparator | Drug: placebo to ramiprilOral placebo treatment to ramipril once daily for 3 years or until progress to next disease level. After progression to next disease level, patients will be unblinded, and ramipril treatment will be initiated. |
| open label ramipril | Other | Drug: RamiprilOpen label treatment with ramipril as per protocol, if randomization is refused. |
Who may qualify
- Ages
- 24 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Definitive diagnosis of Alport syndrome: Kidney biopsy (patient or affected relative/s), and/or mutation analysis (hemizygous X-chromosomal or homozygous autosomal-recessive) and assessment of criteria for clinical diagnosis (haematuria, positive family history regarding kidney diseases, ocular changes, labyrinthine hearing loss)
- Alport syndrome levels 0, I or II at screening (microhaematuria without microalbuminuria or microalbuminuria [30-300 mg albumin/gCrea]) or proteinuria >300 mg albumin/gCrea with GFR>80ml/min). Patients with Alport stage II are not subject to randomization but are treated opel label.
- Aged between ≥24 months and <18 years at screening
- Assent from patient and informed consent from parents/legal guardian
Key exclusion criteria (6 listed)
- Uncertain diagnosis or variants of Alport syndrome such as a heterozygous carrier
- Alport syndrome levels III, or IV (albuminuria >300 mg/g Crea, creatinine clearance <60 mL/min, or end stage renal failure [ESRF])
- Known allergies or intolerances to ramipril or related compounds
- Known contraindication for ACEi-therapy
- Additional chronic renal, pulmonary or cardiac diseases
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 |
|---|---|---|
| RamiprilRamipril (Delix) tablets containing 2.5 mg ramipril, oral application with 1 to 6 mg per body surface area ramipril once daily for 3 years. | Drug | Ramipril blinded |
| placebo to ramiprilOral application of placebo to ramipril, once daily with 1 to 6 mg per body surface area for 3 years or until disease progression. | Drug | placebo to ramipril |
| RamiprilOral treatment with 1 to 6 mg per body surface area ramipril once daily for 3 years as per protocol. | Drug | open label ramipril |
Primary outcome
Time to next disease level
Time frame: within 3 years
Time to progression of Alport Syndrome to the next disease level within 3 years under ramipril treatment compared to placebo, for all randomised patients.
Incidence of Adverse Drug Events before progression
Time frame: within 3 years
Incidence of adverse drug events (ADEs, e.g., angioedema, acute renal failure, hyperkalaemia) under ramipril treatment before disease progression compared to placebo before disease progression, for all randomised patients.
2 secondary outcomes
Albuminuria after three years
Time frame: after 3 years
Adverse Drug Events over three years
Time frame: after 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2020.
- Results publication: PubMed 32299679Gross O, Tonshoff B, Weber LT, Pape L, Latta K, Fehrenbach H, Lange-Sperandio B, Zappel H, Hoyer P, Staude H, Konig S, John U, Gellermann J, Hoppe B, Galiano M, Hoecker B, Ehren R, Lerch C, Kashtan CE, Harden M, Boeckhaus J, Friede T; German Pediatric Nephrology (GPN) Study Group and EARLY PRO-TECT Alport Investigators. A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome. Kidney Int. 2020 Jun;97(6):1275-1286. doi: 10.1016/j.kint.2019.12.015. Epub 2020 Jan 17.
- Derived from this study: PubMed 33159213Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021 Mar;36(3):711-719. doi: 10.1007/s00467-020-04819-6. Epub 2020 Nov 6.
- Derived from this study: PubMed 33040356Boeckhaus J, Hoefele J, Riedhammer KM, Tonshoff B, Ehren R, Pape L, Latta K, Fehrenbach H, Lange-Sperandio B, Kettwig M, Hoyer P, Staude H, Konrad M, John U, Gellermann J, Hoppe B, Galiano M, Gessner M, Pohl M, Bergmann C, Friede T, Gross O; GPN Study Group and EARLY PRO-TECT Alport Investigators. Precise variant interpretation, phenotype ascertainment, and genotype-phenotype correlation of children in the EARLY PRO-TECT Alport trial. Clin Genet. 2021 Jan;99(1):143-156. doi: 10.1111/cge.13861. Epub 2020 Oct 25.
- Derived from this study: PubMed 24529291Ahmed R, Duerr U, Gavenis K, Hilgers R, Gross O. Challenges for academic investigator-initiated pediatric trials for rare diseases. Clin Ther. 2014 Feb 1;36(2):184-90. doi: 10.1016/j.clinthera.2014.01.013.
- Related InformationLink provided by the sponsor.
Related trials for Renal Insufficiency, Chronic
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruiting
An Individuation Intervention to Reduce Socioeconomic Disparities in Chronic Kidney Disease Care
Chronic Kidney Diseases
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.
Oliver Gross, Prof. study chair
University Medical Center Goettingen, Department Nephrology and Rheumatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ramipril in people with Renal Insufficiency, Chronic, run by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH at 1 site in Germany.
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 17 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time to next disease level (time frame: within 3 years). The study lists 2 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 NCT01485978, which also lists 4 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 17 Jun 2020.