Hospitalizations as an outcome measure in COURAGE-ALS

Area of Science:

• Neurology
• Clinical Trials
• Health Services Research

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
• Hospitalizations are significant events in ALS clinical trials, impacting patient outcomes and trial interpretation.
• Characterizing the relationship between hospitalizations and ALS is crucial for accurate endpoint assessment.

Purpose of the Study:

• To develop and validate a methodology for classifying hospitalizations in ALS clinical trials based on their relationship to ALS.
• To apply this classification system in the COURAGE-ALS phase 3 trial of reldesemtiv.
• To analyze hospitalization risk factors in ALS patients.

Main Methods:

• A classification system was developed with ALS clinical trialists to categorize hospitalizations as ALS-related (HR-ALS), unrelated (HU-ALS), or indeterminate (HI-ALS).
• This system was applied by investigators to hospitalizations in the COURAGE-ALS trial.
• Time to first hospitalization and hospitalization incidence were compared between reldesemtiv and placebo groups; risk factors were analyzed.

Main Results:

• The COURAGE-ALS trial was terminated early due to futility.
• Time to first hospitalization and incidence were similar between reldesemtiv and placebo arms (17.6% vs. 18.0%).
• The majority of hospitalizations were classified as HR-ALS (64% placebo, 76% reldesemtiv); bulbar or respiratory onset was a significant risk factor.

Conclusions:

• Most hospitalizations in the COURAGE-ALS trial were related to ALS, but unrelated and indeterminate hospitalizations also occurred.
• Classifying hospitalizations by their relationship to ALS provides valuable data on disease burden and endpoint meaningfulness.
• This methodology enhances the characterization of hospitalizations as clinical trial endpoints in ALS research.