The Chronic Kidney Disease Adaptive Platform Trial Investigating Various Agents for Therapeutic Effect (CAPTIVATE)

• ClinicalTrials.gov Identifier: NCT06058585
• Recruitment Status: Not yet recruiting
• First Posted: September 28, 2023
• Last Update Posted: April 19, 2024
• Sponsor: The George Institute
• Information provided by (Responsible Party): The George Institute

Study Description

Brief Summary:

CAPTIVATE is an international, multi-centre, Phase III, adaptive, platform, randomised controlled trial in people with chronic kidney disease (CKD).

CAPTIVATE aims to find the best treatment, or combination of treatments, that slow the progression of CKD so that fewer people develop kidney failure.

CAPTIVATE provides a research platform that allows many treatment-related questions to be answered within a common trial set-up.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Diseases	Drug: Finerenone; Drug: Placebo Finerenone; Drug: Endothelin Receptor Antagonist; Drug: Placebo Endothelin Receptor Antagonist	Phase 3

Detailed Description:

Chronic kidney disease (CKD) affects over 800 million people globally and is projected to be the 5th most common cause of death by 2040. CKD progresses to kidney failure, increases the risk of early death, heart disease, and leads to a poorer quality of life.

Current treatments do not entirely remove the risk of kidney failure in people with CKD. To improve the outcomes of people with CKD, it is crucial to find the best treatment or combination of treatments that can slow CKD progression. CAPTIVATE aims to address this need.

CAPTIVATE has been designed to test multiple treatments within a common research platform. This design is more efficient and will lead to a shorter time for patients to receive effective treatments. The trial is 'eternal', which means that participants will continue to be recruited for many years until the trial is finally wound up. It is also 'adaptive', providing the flexibility to add new treatments, or remove those that are not working.

Participants can participate in more than one treatment at the same time or at different times. Participants receive each study treatment for 2 years. For each treatment, participants are followed up at study visits that occur at approximately one month, 3 months, 6 months, 12 months, 18 months and 2 years after starting treatment. A final study visit occurs one month after the end of the 2-year treatment phase. Information collected at study visits include blood and urine test results, safety assessments and treatment adherence. Information about the overall health status of each participant is collected every 5 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: Adaptive platform trial evaluating multiple interventions in multiple domains of therapeutic care. Additional interventions and participants will be added as the trial grows.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The default position within CAPTIVATE is that treatment allocations determined by randomisation will be provided on a blinded basis. Blinding, however, may not always be feasible particularly for behavioural or device-related interventions.
• Primary Purpose: Treatment
• Official Title: The Chronic Kidney Disease Adaptive Platform Trial Investigating Various Agents for Therapeutic Effect
• Estimated Study Start Date: June 15, 2024
• Estimated Primary Completion Date: August 30, 2028
• Estimated Study Completion Date: December 31, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Finerenone; Finerenone 10mg or 20mg tablets	Drug: Finerenone; Finerenone 10mg or 20mg tablets, oral, once daily; Other Name: BAY94-8862
Placebo Comparator: Placebo Finerenone; Finerenone matched placebo tablets	Drug: Placebo Finerenone; Finerenone matched placebo tablets, oral, once daily
Experimental: Endothelin Receptor Antagonist	Drug: Endothelin Receptor Antagonist; Oral, once daily
Placebo Comparator: Placebo Endothelin Receptor Antagonist	Drug: Placebo Endothelin Receptor Antagonist; Oral, once daily

Outcome Measures

Primary Outcome Measures :

1. eGFR slope [ Time Frame: From randomisation to week 108 ]
   eGFR slope calculated using eGFR values from randomisation to week 108

Secondary Outcome Measures :

1. Change in albuminuria [ Time Frame: From randomisation to week 24 ]
   Change in albuminuria as measured by uACR (or uPCR if uACR unavailable) between randomisation and 24 weeks, measured as a continuous variable
2. Composite of 40% eGFR decline or kidney failure [ Time Frame: From randomisation to week 108 ]
   Composite outcome of proportion of participants experiencing a 40% eGFR decline between randomisation and 108 weeks, and proportion of participants developing kidney failure (defined as eGFR <15 mL/min/1.73m2 or chronic kidney replacement therapy start) at 108 weeks
3. All-cause mortality at 108 weeks [ Time Frame: 108 weeks ]
   Incidence of death from any cause
4. Number of cardiovascular events [ Time Frame: 108 weeks ]
   Number of cardiovascular events (cardiovascular death, hospitalised heart failure, myocardial infarction, stroke)
5. Safety and tolerability of treatment [ Time Frame: 108 weeks ]
   Incidence and rates of adverse events, and time from commencement of study treatment until interruption of treatment due to toxicity.
6. Change in quality of life [ Time Frame: From randomisation to week 108 ]
   Change in quality of life measured using the Quality of Life Impact Survey for Kidney Disease (QDIS-CKD) at 6-monthly intervals from randomisation to week 108

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Known chronic kidney disease from any cause (eGFR ≥25 mL/min/1.73m2)
3. Currently receiving standard of care treatment according to treating physician
4. Eligible for randomisation in at least one recruiting domain-specific appendix
5. Participant and treating physician are willing and able to perform trial procedures

Exclusion Criteria:

1. Planned to commence kidney replacement therapy or kidney transplant surgery in next 6 months
2. Life expectancy less than 6 months

Contacts and Locations

Contacts

Contact: Enmoore Lin; 61 2 8052 4511; captivate@georgeinstitute.org.au

Sponsors and Collaborators

The George Institute

Investigators

• Study Chair: Sradha Kotwal; The George Institute
• Study Chair: Hiddo Lambers Heerspink; The George Institute

More Information

• Responsible Party: The George Institute
• ClinicalTrials.gov Identifier: NCT06058585
• Other Study ID Numbers: P01351
• First Posted: September 28, 2023
• Last Update Posted: April 19, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Trial data will be made available as a resource for future unspecified research, subject to any prior contractual obligations. Researchers wishing to gain access to the study resources will be required to submit an application for review by the Platform Oversight Committee, including a detailed project description, a list of data requested, and evidence of ethical approval. De-identified data extracts will be made available to approved proposals, and will not include data obtained from data linkage with local registries.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: TBC
• Access Criteria: Assessments of data requests will be based on sound science, benefit-risk balancing and research team expertise.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The George Institute:

Chronic kidney disease; Mineralocorticoid Receptor Antagonist; Finerenone

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Endothelin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action