Integrating liver endpoints in clinical trials of cardiovascular and kidney disease

Area of Science:

• Cardiology
• Nephrology
• Hepatology
• Metabolic Disorders

Background:

• Cardiovascular disease, metabolic disorders, and chronic kidney disease present complex clinical challenges.
• Metabolic-dysfunction-associated steatotic liver disease (MASLD) frequently co-occurs with these conditions, sharing common risk factors and mechanisms.
• Excluding patients with MASLD from clinical trials limits understanding of potential cross-disease therapeutic benefits.

Purpose of the Study:

• To advocate for the inclusion of patients with MASLD in cardio-kidney-metabolic clinical trials.
• To emphasize the importance of measuring liver outcomes in these trials.
• To explore the implications for clinical trial design and regulatory pathways.

Main Methods:

• This perspective paper reviews existing evidence on shared mechanisms between MASLD and cardio-kidney-metabolic diseases.
• It discusses the rationale for including MASLD patients in relevant clinical trials.
• It outlines considerations for trial design, safety monitoring, and regulatory approval.

Main Results:

• New therapies may offer benefits across cardiovascular, kidney, metabolic, and liver diseases.
• Exclusion of MASLD patients hinders the discovery of these broad therapeutic effects.
• Including MASLD patients requires careful consideration of trial design and safety.

Conclusions:

• Integrating MASLD patients into cardio-kidney-metabolic trials is essential for comprehensive therapeutic development.
• This approach necessitates robust safety monitoring and adapted regulatory strategies.
• Future clinical trial conduct should embrace this inclusive paradigm to advance patient care.