FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC): study protocol for randomized controlled trial

Abstract

Background: Fimasartan is the ninth angiotensin receptor blocker to be developed. However, it has not yet been evaluated for reno-protective effects in hypertensive diabetic chronic kidney disease (CKD). The target blood pressure (BP) for hypertensive diabetic CKD is also a controversial topic. This trial was designed to assess the reno-protective effects of fimasartan compared to those of losartan as a primary outcome. This study also compares the two drugs with regard to cardiovascular and renal outcomes in accordance with target systolic BP (SBP) (as secondary outcomes).

Methods: This study is a prospective, phase III, randomized, double-blind, active-controlled, non-inferiority, four-parallel group, dose-titration, multicenter trial. We recruit patients with hypertensive diabetic CKD with overt proteinuria. Participants will be randomized into four groups (1:1:1:1): fimasartan standard SBP control (SBP < 140 mmHg); fimasartan strict SBP control (SBP < 130 mmHg); losartan standard SBP control; and losartan strict SBP control. After 24 weeks, all individuals are treated with fimasartan for an additional 120 weeks in an open-label design, maintaining their assigned SBP control groups as randomized. The primary endpoint is the rate of change in proteinuria, which is assessed using the spot urine albumin-creatinine ratio at 24 weeks. The secondary endpoints are the cardiovascular and renal outcomes at 144 weeks compared between the strict SBP and standard SBP control groups.

Discussion: The FANTASTIC is a clinical study to provide: (1) the reno-protective effect of fimasartan; and (2) the target BP to reduce adverse outcomes in hypertensive diabetic CKD with overt proteinuria.

Trial registration: Clinicaltrials.gov, NCT02620306. Registered on 1 December 2015.

Keywords: Chronic kidney disease; Diabetes mellitus; Hypertension; Proteinuria.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by MFDS (Ministry of Food and Drug Safety) which is a regulatory authority in the Republic of Korea (reference no. 30626). This study has obtained relevant IRB approval at the 40 sites intended to participate in recruitment: Gachon University Gil Medical Center IRB (GCIRB2015-282, GCIRB2015-283); The Catholic University of Korea Seoul St. Mary’s Hospital IRB (KC15MDMT0752); Kyung Hee University Hospital at Gangdong IRB (KHNMC 2015-10-001, KHNMC 2015-10-002); Kangbuk Samsung Hospital IRB (KBSMC 2015-10-010); Kyungpook National University Hospital IRB (KNUH 2015-10-008); Korea University Anam Hospital IRB (ED15223); National Health Insurance Service Ilsan Hospital IRB (NHIMC 2015-09-007); Dongguk University Ilsan Hospital IRB (2015–105, 2015–106); Seoul National University Bundang Hospital IRB (B-1510/319-001, B-1510/319-002); Seoul National University Hospital IRB (H-1510-051-710, H-1510-052-710, H-1612-076-814); Seoul Medical Center IRB (2015–083); Severance Hospital IRB (4-2015-0848); Ulsan University Hospital IRB (UUH 2015-10-005); Yonsei University Wonju Severance Christian Hospital IRB (CR115050-051, CR115051-052); Ewha Woman’s University Mokdong Hospital IRB (EUMC 2015-09-019, EUMC 2015-09-020); Inje University Ilsan Paik Hospital IRB (ISPAIK 2015-10-013, ISPAIK 2016-05-010, ISPAIK 2016-12-018); Chonnam National University Hospital IRB (CNUH-2015-217); Chungnam National University Hospital IRB (CNUH 2015-10-006, CNUH 2015-10-012); Hanyang University Seoul Hospital IRB (HYUH 2015-09-018); SMG - SNU Boramae Medical Center IRB (20160524/26-2016-61/062); The Catholic University of Korea Incheon St. Mary’s Hospital IRB (OC16MDMT0083); Hallym University Medical Center IRB (2016-S039); Pusan National University Hospital IRB (H-1605-017-056); Chung-Ang University Hospital IRB (C2016137(1880)); Konkuk University Hospital IRB (KHU1010824); Samsung Medical Center IRB (SMC 2016-12-051); Ajou University Hospital IRB (AJIRB-MED-CT3-16-474); Inje University Sanggye Paik Hospital IRB (SGPAIK 2016-12-005); Chosun University Hospital IRB (CHOSUN 2016-12-010). All participants provide informed consent before enrollment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Flow chart of FANTASTIC study. The FANTASTIC study consists of two phases: four-parallel double-blind period to investigate the reno-protective effect of fimasartan and two-parallel open-label period for prognosis in accordance with target BP. a Standard BP control group (systolic BP < 140 mmHg). b Strict BP control group (systolic BP < 130 mmHg). FIM fimasartan, LOS losartan, CCB calcium channel blocker, ACR albumin–creatinine ratio, CV cardiovascular, SBP systolic blood pressure

Fig. 2

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) figure. BP blood pressure, BUN blood urea nitrogen, ECG electrocardiography, eGFR estimated glomerular filtration rate