% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Rudnicki:281786,
      author       = {Rudnicki, Stacy A and Al-Chalabi, Ammar and Andrews, Jinsy
                      A and Chio, Adriano and Corcia, Philippe and Couratier,
                      Philippe and Cudkowicz, Merit E and De Carvalho, Mamede and
                      Genge, Angela and Hardiman, Orla and Heiman-Patterson, Terry
                      and Henderson, Robert D and Ingre, Caroline and Johnston,
                      Wendy and Ludolph, Albert and Maragakis, Nicholas J and
                      Miller, Timothy M and Mora, Jesus S and Petri, Susanne and
                      Simmons, Zachary and Van Den Berg, Leonard H and Zinman,
                      Lorne and Herder, Katherine E and Kupfer, Stuart and Malik,
                      Fady I and Meng, Lisa and Simkins, Tyrell J and Wei, Jenny
                      and Wolff, Andrew A and Shefner, Jeremy M},
      collaboration = {group, Courage-Als study},
      title        = {{H}ospitalizations as an outcome measure in
                      {COURAGE}-{ALS}.},
      journal      = {Amyotrophic lateral sclerosis $\&$ frontotemporal
                      degeneration},
      volume       = {26},
      number       = {7-8},
      issn         = {2167-8421},
      address      = {Abingdon},
      publisher    = {Taylor Francis Group},
      reportid     = {DZNE-2025-01179},
      pages        = {802 - 811},
      year         = {2025},
      abstract     = {Objective: To describe the development of a methodology to
                      characterize hospitalizations and their relationship to
                      amyotrophic lateral sclerosis (ALS) and provide results
                      using this process in a phase 3 trial of reldesemtiv in ALS.
                      Methods: ALS clinical trialists assisted in developing a
                      classification system to determine if a hospitalization was
                      related to ALS (HR-ALS), unrelated (HU-ALS), or if the
                      relationship was indeterminate (HI-ALS) and this was applied
                      by the investigators to hospitalizations in COURAGE-ALS.
                      Time to first hospitalization and number of hospitalizations
                      were compared between those assigned reldesemtiv or placebo
                      for up to 48 weeks. Demographic and clinical features were
                      evaluated for prediction of hospitalization risk; this
                      analysis was limited to those participants who completed the
                      first 24-week double-blind placebo-controlled portion of the
                      trial. Results: COURAGE-ALS terminated early due to
                      futility. Time to first hospitalization was similar in the
                      reldesemtiv compared to placebo arms as was the incidence,
                      with 86 of the participants $(17.6\%$ of those originally
                      assigned placebo and $18.0\%$ originally on reldesemtiv)
                      experiencing an event. The largest percentage of events was
                      classified as HR-ALS for both placebo $(64\%,$ 18/28) and
                      reldesemtiv $(76\%,$ 44/58). In a multivariate model, only
                      bulbar or respiratory onset disease was a significant risk
                      factor for hospitalization. Conclusion: While most
                      hospitalizations in COURAGE-ALS were HR-ALS, HU-ALS and
                      HI-ALS also occurred. When using hospitalization as an
                      endpoint in an ALS clinical trial, recording its
                      relationship to ALS provides additional details to
                      characterize disease burden and clinical meaningfulness of
                      the endpoint.},
      keywords     = {Humans / Amyotrophic Lateral Sclerosis: drug therapy /
                      Amyotrophic Lateral Sclerosis: therapy / Amyotrophic Lateral
                      Sclerosis: diagnosis / Amyotrophic Lateral Sclerosis:
                      epidemiology / Hospitalization: statistics $\&$ numerical
                      data / Male / Female / Middle Aged / Double-Blind Method /
                      Aged / Outcome Assessment, Health Care: methods /
                      Amyotrophic lateral sclerosis (Other) / COVID-19 (Other) /
                      fast skeletal muscle troponin activator (Other) /
                      hospitalization (Other) / motor neuron disease (Other) /
                      reldesemtiv (Other)},
      cin          = {Clinical Study Center (Ulm)},
      ddc          = {610},
      cid          = {I:(DE-2719)5000077},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40503807},
      doi          = {10.1080/21678421.2025.2515907},
      url          = {https://pub.dzne.de/record/281786},
}