Prognostic Enrichment Design in Clinical Trials for Autosomal Dominant Polycystic Kidney Disease
| Autor: | Wen Zhou, Eiji Higashihara, Peter C. Harris, Maria V. Irazabal, John Ouyang, Jaime D. Blais, Ronald D. Perrone, Frank S. Czerwiec, Vicente E. Torres, Arlene B. Chapman, Ron T. Gansevoort, Olivier Devuyst |
|---|---|
| Přispěvatelé: | Cardiovascular Centre (CVC), Groningen Kidney Center (GKC) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
medicine.medical_specialty
CYST GROWTH 030232 urology & nephrology Urology Autosomal dominant polycystic kidney disease Tolvaptan Renal function Kidney Volume SIROLIMUS lcsh:RC870-923 V2 RECEPTOR ANTAGONIST law.invention 03 medical and health sciences 0302 clinical medicine disease progression Randomized controlled trial Clinical Research law Internal medicine kidney volume medicine Journal Article Cyst 030212 general & internal medicine TOLVAPTAN mouse clinical trials model autosomal dominant polycystic kidney disease business.industry lcsh:Diseases of the genitourinary system. Urology medicine.disease image classification of ADPKD Clinical trial LONG-ACTING SOMATOSTATIN Endocrinology Nephrology Population study business medicine.drug |
| Zdroj: | Kidney International Reports, Vol 1, Iss 4, Pp 213-220 (2016) Kidney International Reports Kidney International Reports, 1(4), 213-220. ELSEVIER SCIENCE INC |
| ISSN: | 2468-0249 |
| Popis: | Introduction: Patients with slowly progressive autosomal dominant polycystic kidney disease (ADPKD) are unlikely to experience outcomes during randomized controlled trials (RCTs). An image classification of ADPKD into typical (diffuse cyst distribution) class 1A to E (by age- and height-adjusted total kidney volume [TKV]) and atypical (asymmetric cyst distribution) class 2 was proposed for prognostic enrichment design, recommending inclusion of only classes 1C to 1E in RCTs.Methods: A post hoc exploratory analysis was conducted of the TEMPO 3:4 Trial, a prospective, randomized, double-blinded, controlled clinical trial in adult subjects with ADPKD, an estimated creatinine clearance >60 ml/min and total kidney volume >750 ml.Results: Due to the entry criteria, the study population of TEMPO 3:4 was enriched for classes 1C-E (89.5 % of 1436 patients with baseline magnetic resonance images) compared to unselected populations (e.g., 60.5% of 590 Mayo Clinic patients). The effects of tolvaptan on TKV and eGFR slopes were greater in classes 1C to E than in 1B. In TEMPO 3:4, tolvaptan reduced TKV and eGFR slopes from 5.51% to 2.80% per year and from -3.70 to -2.78 ml/min/1.73 m(2) per year, and lowered the risk for a composite endpoint of clinical progression events (hazard ratio = 0.87). Restricting enrollment to classes 1C to E would have reduced TKV and eGFR slopes from 5.78% to 2.91% per year and from -3.93 to -2.82 ml/min/1.73 m(2) per year, and the risk of the composite endpoint (hazard ratio = 0.84, P = 0.003), with 10.5% fewer patients.Discussion: Prognostic enrichment strategies such as the entry criteria used for TEMPO 3:4 or preferably the proposed image classification should be used in RCTs for ADPKD to increase power and to reduce cost. |
| Databáze: | OpenAIRE |
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