Proteomic Prediction and Renin Angiotensin Aldosterone System Inhibition Prevention Of Early Diabetic nephRopathy In TYpe 2 Diabetic Patients With Normoalbuminuria (PRIORITY)
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|ClinicalTrials.gov Identifier: NCT02040441|
Recruitment Status : Completed
First Posted : January 20, 2014
Last Update Posted : December 21, 2018
This is a prospective, multicenter, randomized, double blind, placebo-controlled and a prospective observational study.
This study will be conducted at 15 study centers in various European countries. 1777 participant between 18 to 75 years old with Type 2 diabetes mellitus and normoalbuminuria participate in the study. The study period is 2 - 4.5 years (excluding the 6 week screening period). Depending on the risk score of the urinary protein pattern, participants have been stratified into an observational group or an interventional group. Participants with the low risk pattern (observational group) attend visits annually after screening and baseline. Participants with the high risk pattern (interventional group) attend study visits every 13 weeks after screening and baseline.
The interventional group has been allocated into one treatment group either receiving spironolactone or placebo. A placebo is a medicine without a pharmaceutical substance. The allocation to one of the two treatment groups has been done by a random distribution procedure established before the study start.
The results of the urine sample from the Screening visit has been analysed and the urine proteomic pattern is determined to be either low- or high risk pattern and will determine the further study program.
Participants with a low-risk pattern (observational group):
During the study period, participants attend an annual project visit, were regular diabetes care is performed and three urine samples are analysed for albuminuria.
Participants with a high-risk pattern (intervention group):
Participants with a high-risk pattern have been randomized to either spironolactone treatment or placebo. The treatment is one tablet for oral use to be taken once a day for the entire study period. Four times each year (every 13th week) a study visit is conducted including examination of three urine samples for albuminuria.
This study aims to:
- Confirm in a prospective multicenter study of normoalbuminuric type 2 DM patients that the urinary proteome test identifies patients with a high risk for development of microalbuminuria.
- Demonstrate the clinical utility of the test by showing that aldosterone blockade in high-risk patients can reduce progression to microalbuminuria in comparison to placebo, on the top of standard treatment in a randomized double-blind, placebo-controlled multicenter study.
|Condition or disease||Intervention/treatment||Phase|
|Diabetic Nephropathy Diabetic Retinopathy||Drug: Spironolactone Drug: Placebo Drug: Standard care||Phase 2 Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1777 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Proteomic Prediction and Renin Angiotensin Aldosterone System Inhibition Prevention Of Early Diabetic nephRopathy In TYpe 2 Diabetic Patients With Normoalbuminuria|
|Actual Study Start Date :||March 2014|
|Actual Primary Completion Date :||November 2018|
|Actual Study Completion Date :||November 2018|
Active Comparator: Spironolactone
High-risk pattern: Spironolactone 25 mg once daily + Standard care
Drug: Standard care
Standard diabetes care
Placebo Comparator: Placebo
High-risk pattern: One placebo tablet once daily + Standard care
Drug: Standard care
Standard diabetes care
Low-risk pattern: Standard care
Drug: Standard care
Standard diabetes care
- Albuminuria [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]Development of confirmed microalbuminuria (UACR >30 mg/g) in at least two out of three first morning voids with ≥ 30% increase (geometric mean) in UACR from "run-in" period samples OR > 40 mg/g (geometric mean).
- Cardiovascular disease and mortality [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]Comparison of composite fatal and non-fatal cardiovascular outcome (myocardial infarction, stroke, coronary artery bypass, coronary re-vascularisation, hospitalization for heart failure and cardiovascular death), and all-cause mortality during the study.
- Retinopathy [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]Comparison of incidence of retinopathy and frequency of laser treatment. Data collected from self-reported adverse events.
- Change in albuminuria [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]In addition to the categorical analysis of urinary albumin excretion, an analysis will be performed with changes in geometric mean albuminuria throughout the study period in all patients by assessing the slope of albuminuria changes and absolute changes from inclusion to end of trial
- Microalbuminuria [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]Development of microalbuminuria (UACR >30 mg/g) in at least one morn-ing void urine sample will be used as a secondary outcome instead of con-firmed microalbuminuria
- Macroalbuminuria [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]Development of macroalbuminuria (UACR >300 mg/g) in 2 out 3 first morning void urine samples)
- Change in CKD class [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]For patients with estimated GFR ≥ 60 at baseline, development of estimated GFR<60 ml/min/1.73m2. Estimated GFR will be measured from serum creatinine (standard-ized traceable method) on blood samples tested in local laboratories.
- Slope of estimated GFR [ Time Frame: Screening, (Low-risk: year 1, 2 and 3), (high-risk: week 13, 26, 39, 52, 65, 78, 91, 104, 117, 130, 143, 156) ]Change in estimated GFR (slope and absolute from baseline and from 3 month post-baseline to end of study)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02040441
|Institut Klinické a Experimentální Mediciny|
|Universita Karlova v Praze|
|Steno Diabets Center Copenhagen|
|Gentofte, Denmark, 2820|
|Universitätsklinikum Carl Gustav Carus, Technischen Universität Dresden|
|Klinikum St. Georg gGmbH|
|Geniko Nosikomeico Athinas Ippokrateio, Hospital Diabetes Center|
|Instituto de Ricerche Farmacologiche Mario Negri|
|Bergamo, Italy, 24020|
|Macedonia, The Former Yugoslav Republic of|
|Department of Nephrology, University of Skopje|
|Skopje, Macedonia, The Former Yugoslav Republic of|
|University Medical Center Groningen|
|Diabetes Vascular Research Foundation|
|Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz|
|Madrid, Spain, 28040|
|University of Glasgow|
|Glasgow, United Kingdom, G12 8TA|
|Study Chair:||Peter Rossing, Prof. MD||Steno Diabetes Center|
|Principal Investigator:||Matias Trillini, MD||Istituto de Ricerche Farmacologiche Mario Negri|
|Principal Investigator:||Alberto Ortiz, MD||Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz|
|Principal Investigator:||Christian Delles, MD||University of Glasgow|
|Principal Investigator:||Gerjan Navis, MD||University Medical Center Groningen|
|Principal Investigator:||Ivan Rychlik, MD||Univerzita Karlova v Praze|
|Principal Investigator:||Joachim Beige, MD||Klinikum St. Georg gGmbH|
|Principal Investigator:||Marina Noutsou, MD||Geniko Nosikomeico Athinas Ippokrateio, Hospital Diabetes Center|
|Principal Investigator:||Peter Girman, MD||Institut Klinické a Experimentální Mediciny|
|Principal Investigator:||Goce Spasovski, MD||Department of Nephrology, University of Skopje|
|Principal Investigator:||Adriaan Kooy, MD||Diabetes Vascular Research Foundation Hoogeveen|
|Principal Investigator:||Marjin Speeckaert, MD||Universitair Ziekenhuis Gent|
|Principal Investigator:||Joline Beulens, MD||Stichting VUMC|
|Principal Investigator:||Rüdiger Göke, MD||Diabetologen Hessen|
|Principal Investigator:||Andreas Birkenfeld, MD||Universitätsklinikum Carl Gustav Carus, Technischen Universität Dresden|