Dose Recommendations for Drugs in Patients With Liver Cirrhosis (The ALIVe Study): Protocol for a Multiphase Validation and Consensus Study.

BACKGROUND: Liver cirrhosis leads to an impaired liver function with reduced metabolic capacity, which affects the pharmacokinetics of several drugs, requiring dose adjustments. Although limited literature provides guidance on appropriate administration of drugs in cirrhosis, no guidelines currently exist for dose selection or adjustment.

OBJECTIVE: The objective of this study is to provide guidance on the selection, dosing, and appropriate use of drugs in patients with liver cirrhosis and evaluate the clinical application of these recommendations.

METHODS: Three steps are planned to establish dose recommendations for patients with liver cirrhosis. First, a systematic literature search will be conducted to identify specific recommendations for drug selection and dosing in cirrhosis, and the literature will be assessed for reporting quality and evidence level. Subsequently, the resulting recommendations will undergo an internal preassessment procedure for relevance of the covered drugs with regard to availability, the clinical impact of adverse drug reactions, the frequency of use, and the expected benefit of dose adjustment. Second, a modified Delphi procedure will be conducted to (1) analyze the clinical handling of the identified drugs by experts in clinical practice in a first round and (2) parse changes resulting from the inclusion of medication-related information and further harmonize differing dose recommendations in a second round. Finally, the adopted dose recommendations will be implemented in a clinical study involving patients with liver cirrhosis to analyze the impact of the recommendations on patient safety.

RESULTS: The planned clinical validation phase started in January 2025 and is currently underway. As of May 2026, 121 patients have been enrolled. Statistical analyses will be conducted in accordance with the predefined analysis plan. Findings from the literature review, the Delphi consensus process, and the clinical validation phase will be reported in subsequent publications. Final study results and data analysis are anticipated in August 2026.

CONCLUSIONS: This protocol outlines a structured approach combining a systematic literature review of specific dose recommendations in patients with cirrhosis that integrates a quality assessment to ensure the inclusion of only high-quality evidence, expert opinions through a Delphi consensus aligning differing recommendations, and a clinical validation to support safer drug therapy in patients with liver cirrhosis.

© Katharina Karsten Dafonte, Philipp Lutz, Christian Jansen, Christian P Strassburg, Robert Németh, Gunther Hartmann, Ulrich Jaehde, Martin Coenen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org).

PMID: 42265867