The Global Kidney Patient Trials Network and the CAPTIVATE Platform Clinical Trial Design
Authors: Kotwal Sradha S. , Perkovic Vlado , Jardine Meg J. , Kim Dana , Shah Nasir A. , Lin Enmoore , Coggan Sarah , Billot Laurent , Vart Priya , Wheeler David C. , de Boer Ian H. , Zhang Hong , Hou Fan Fan , Sugawara Yuka , Marion Joseph , Lewis Roger J. , Berry Lindsay R. , McGlothlin Anna , Jha Vivekanand , De Nicola Luca , Gorriz Jose L. , Heerspink Hiddo J. L. ,   GKPTN and CAPTIVATE Investigators, Alvarisqueta Andres , Bittar Julio , Cluigt Natalia , Gaite Judith , Gaite Luis , Maurich Silvia Marcela , Ramallo Pablo , Quevedo Alejandra , Arias Carlos , Resk Jorge Hector , Brusa Mariana , Marioli Paula Andrea , McMahon Lawrence , Govindarajulu Sridevi , Gray Nicholas , Roger Simon , Flavell Adam , Swaminathan Suda , Toussaint Nigel , Stranks Jessica , Mah Peak Mann , Vora Parind , Cournoyer Serge , Langlois Marie-France , Weir Matthew , Hou Fan Fan , Zhang Hong , Liu Zhihong , Caili Wang , Qun Luo , Yaozhong Kong , Ping Fu , Zuying Xiong , Wanhong Lu , Guisen Li , Chen Menghua , Peng Li , Liu Yiwen , Hong Cheng , Wang Jianqin , Junwu Dong , Zhigang Ma , Rui Yan , Yongjun Shi , Chun Zhang , Xueai Lv , Xiaoyong Yu , Xueyan Bian , Bai Yihua , Ravera Maura , Pisani Antonio , Gregorini Mariacristina , Esposito Ciro , Aucella Filippo , De Nicola Luca , Nappi Felice , Abaterusso Cataldo , Gesualdo Loreto , Andreucci Michele , Simeoni Mariadelina , Itano Seiji , Kashihara Naoki , Wada Jun , Sugawara Yuka , Nangaku Masaomi , Naka Motoji , Takai Masahiko , Goto Shin , Narita Ichei , Fukagawa Masafumi , Yokoo Takashi , Kaname Shinya , Masanori Abe , Suzuki Yusuke , Soler Romeo María Jose , Pardo Emma , Soto Gonzalez Alfonso , Cruzado Josep Maria , Górriz Jose Luis , Cigarran Secundino , Cereto Castro Fernando , Pantoja Perez Jonay , Morales Portillo Cristobal , Tinahones Maduen Francisco Jose , Marques Maria , Pecoits-Filho Roberto , Rovner Sergio , Arif Ahmed , Pergola Pablo , Tran Tuan-Huy , Montero     Manuel , Hammoud Jamal , Shanik Michael , Velasquez-Mieyer Pedro Andres , Lucas Katherine Jean , Franklin James , Green Arthur , Drabick Andrew , Alello Joseph , Busch Robert , Patel Nina , Vora Sanjay , Brusco Osvaldo A. , Gomez-Cortez Jose , Kovesdy Csaba , de Boer Ian , Alicic Radica , Kirk Eric , Shahid Nauman , Reddy Anand , Hernandez Pedro , Mayfield Ronald , Schneider Linda , Layden Brian , Bueso Gerard , Yu Margaret , Malhotra Vinod , Hour Billy , Kaveh Kianoosh , Numrungroad Visal , Gohh Reginald , Santiago Jose , Dwivedi Shaunak , Ong Steven , Edris Marwan , Desai Anant , Gold Marina , Wieskopf Bram , Kotwal Sradha , Lambers Heerspink Hiddo , Lin Enmoore , Coggan Sarah , Hossain Farjarneh , Sun Shengkun , Hsu Fan Han , Dombroski Emma , Ali Maria , Cambon Luc , Yap Ling , Ly Mai , Chua Justine , Mounsey Dominic , Tsukada Naomi , Yoffe Alina , Achiaga Francisco , Mok Clara , Walker Emily , Reid Ann , Johnstone Masego , Czank Charles , Rominger Lisa , Cisternas Paula , Rizzi Daniel , Ola Joy , Garcia David , Cox Jessica , Nelson Osha , Hones Lyndal , Ho Melinda , Tutt Melissa , Beusenberg Fred , Kanade Radhika , Raymond Eunice , Hamilton Ron , Adeyari Christine , Zheng Yuehan , Chow Joyce , Pollard Stephanie , Chiari Enrico , Cabrerizo Olga , Bowman Denison , Xiao Yiping , Bai Xuejie , Zhou Joe , Lokesh Divya , Larsheid Larry , Shabbir Naveed , Hurndon Dana , Garmack Renee , Shilpakar Liza , Casulla Jennifer , Cha Hui Ping , Jin HyeRyun , Lickey Diane , Long Jin , Bie Lingling , Monaghan Helen , Arnott Clare , di Tanna Gian Luca , Grey Vicky , Krishnasamy Rathika , Guinness Dean , Halewood Jeremy , Ioasa David , He Zhangyi , Hossain Farjaneh , Varley Ben , Don Sima , Zulkhernain Nursafwana (Saffy) , Kim Michelle , Gregory Victoria 
Published: December 2024

Importance

Chronic kidney disease (CKD) is a global health priority affecting almost 1 billion people. New therapeutic options and clinical trial innovations such as adaptive platform trials provide an opportunity to efficiently test combination therapies.

Objective

To describe the design and baseline results of the Global Kidney Patient Trials Network (GKPTN) and the design and structure of the global adaptive platform clinical trial Chronic Kidney Disease Adaptive Platform Trial Investigating Various Agents for Therapeutic Effect (CAPTIVATE) to find new therapeutic options and treatments for people with kidney disease.

Design, Setting, and Participants

The GKPTN is a multicenter registry that started in May 2020 and is ongoing, while CAPTIVATE is a multicenter, multifactorial, phase 3, placebo-controlled adaptive platform randomized clinical trial that includes patients with CKD. The first participant was randomized in September 2024. The GKPTN recruits patients from kidney and endocrinology practices, and CAPTIVATE aims to recruit patients from GKPTN sites where possible. Both the GKPTN and CAPTIVATE recruit patients with nondialysis CKD.

Intervention

CAPTIVATE will test several investigational agents or combinations of agents, beginning with a mineralocorticoid receptor antagonist.

Main Outcomes and Measures

The GKPTN monitors clinical characteristics, treatment, and outcomes to identify eligible clinical trial participants and provide a contemporary global picture of patients with CKD. The primary outcome of CAPTIVATE is to identify investigational agents or combinations of agents to reduce the rate of chronic estimated glomerular filtration rate (eGFR) decline. The default maximum sample size per treatment arm in each domain, based on bayesian simulations, is 500 participants, providing approximately 90% power to detect a clinically meaningful improvement of 2.6 mL/min/1.73 m2 in eGFR at the end of the 104-week study period.

Results

The GKPTN has enrolled 4334 patients across 119 sites in 8 countries (US, Australia, Argentina, China, Italy, Canada, Spain, and Japan). The mean (SD) participant age at enrollment was 64.5 (16.2) years, 2542 participants (58.7%) were female, and diabetic kidney disease was most frequently reported among patients for CKD etiology (1875 [43.3%]). Among the participants, the mean (SD) eGFR was 52.9 (29.3) mL/min/1.73 m2, and the median urinary albumin-to-creatinine ratio was 89 mg/g (coefficient of variation, 20-420 mg/g). In the GKPTN cohort, the mean eGFR decline was steeper among participants with a baseline eGFR of 60 mL/min/1.73 m2 or more (−2.29 [95% CI, −3.14 to −1.44]) compared with those with an eGFR of less than 60 mL/min/1.73 m2 (−1.16 [95% CI, −1.77 to −1.44]) and was progressively steeper in more severe albuminuria subgroups.

Conclusions and Relevance

The GKPTN registry and the CAPTIVATE trial have the potential to expand and optimize therapeutic options for people with CKD using an adaptive platform clinical trial design.

Trial Registration

ClinicalTrials.gov Identifiers: NCT04389827 and NCT06058585