Sodium oxybate for the maintenance of abstinence in alcohol-dependent patients: An international, multicenter, randomized, double-blind, placebo-controlled trial
Julien Guiraud, Giovanni Addolorato, Mariangela Antonelli, Henri‐Jean Aubin, Andrea de Bejczy, Amine Benyamina, Roberto Cacciaglia, Fabio Caputo, Maurice Demattéis, Anna Ferrulli, Anna E. Goudriaan, Antoni Gual, Otto‐Michael Lesch, Icro Maremmani, Antonio Mirijello, David Nutt, François Paillé, Pascal Perney, Roch Poulnais, Quentin Raffaillac, Jürgen Rehm, Benjamin Rolland, Claudia Rotondo, Bruno Scherrer, Nicolas Simon, Katrin Skala, Bo Söderpalm, Lorenzo Somaini, Wolfgang H. Sommer, Rainer Spanagel, Gabriele Vassallo, Henriette Walter, Wim van den Brink
Abstract
Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423