Sodium oxybate for the maintenance of abstinence in alcohol-dependent patients: An international, multicenter, randomized, double-blind, placebo-controlled trial.


Journal

Journal of psychopharmacology (Oxford, England)
ISSN: 1461-7285
Titre abrégé: J Psychopharmacol
Pays: United States
ID NLM: 8907828

Informations de publication

Date de publication:
Oct 2022
Historique:
pubmed: 8 7 2022
medline: 12 10 2022
entrez: 7 7 2022
Statut: ppublish

Résumé

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. To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. 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. 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; Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. ClinicalTrials.gov Identifier: NCT04648423.

Sections du résumé

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;
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.

Identifiants

pubmed: 35796481
doi: 10.1177/02698811221104063
pmc: PMC9548946
doi:

Substances chimiques

Ethanol 3K9958V90M
Sodium Oxybate 7G33012534

Banques de données

ClinicalTrials.gov
['NCT04648423']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1136-1145

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Auteurs

Julien Guiraud (J)

Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
D&A Pharma, Paris, France.

Giovanni Addolorato (G)

Alcohol Use Disorder and Alcohol Related Disease Unit, Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Internal Medicine Unit, Columbus-Gemelli Hospital, Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Mariangela Antonelli (M)

Internal Medicine Unit, Columbus-Gemelli Hospital, Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Henri-Jean Aubin (HJ)

French Institute of Health and Medical Research (Inserm), Centre de Recherche en Epidémiologie et Santé des Populations (CESP), Universite Paris-Saclay, Villejuif, France.
Addiction Research and Treatment Center, Paul Brousse Hospital, Paris-Sud University, Villejuif, France.

Andrea de Bejczy (A)

Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden.

Amine Benyamina (A)

Addiction Research and Treatment Center, Paul Brousse Hospital, Paris-Sud University, Villejuif, France.

Roberto Cacciaglia (R)

Laboratorio Farmaceutico CT, San Remo, Italy.

Fabio Caputo (F)

Department of Internal Medicine, SS. Annunziata Hospital, Cento (Ferrara), University of Ferrara, Italy.
Centre for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy.

Maurice Dematteis (M)

Department of Addiction Medicine, Grenoble-Alpes University Hospital, and Faculty of Medicine, Grenoble Alpes University, France.

Anna Ferrulli (A)

Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy.
Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.

Anna E Goudriaan (AE)

Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Arkin, Department of Research and Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.

Antoni Gual (A)

Psychiatry Department, Neurosciences Institute, Hospital Clinic, IDIBAPS, Barcelona, Spain.

Otto-Michael Lesch (OM)

University Clinic of Psychiatry and Psychotherapy, Department of Social Psychiatry, Medical University of Vienna, Austria.

Icro Maremmani (I)

Santa Chiara University Hospital, University of Pisa, Italy.

Antonio Mirijello (A)

Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza General Hospital, San Giovanni Rotondo (FG), Italy.

David J Nutt (DJ)

Centre for Neuropsychopharmacology, Imperial College London, United Kingdom.

François Paille (F)

Department of Addiction Treatment, University Hospital, Vandoeuvre-lès-Nancy, France.

Pascal Perney (P)

Addiction Medicine, CHU Nîmes, France.

Roch Poulnais (R)

D&A Pharma, Paris, France.

Quentin Raffaillac (Q)

D&A Pharma, Paris, France.

Jürgen Rehm (J)

Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Psychiatry, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Clinical Psychology & Psychotherapy Technical University Dresden, Dresden, Germany.
Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

Benjamin Rolland (B)

SUAL, HCL, CH Le Vinatier; Univ Lyon; UCBL; INSERM U1028; CNRS UMR5292, Centre de Recherche en Neuroscience de Lyon (CRNL), Bron, France.

Claudia Rotondo (C)

Centro di Riferimento Alcologico della Regione Lazio (CRARL), Dipartimento di Salute Mentale, Roma, Italy.

Bruno Scherrer (B)

Bruno Scherrer Conseil, Saint Arnoult en Yvelines, France.

Nicolas Simon (N)

Aix Marseille Univ, APHM, INSERM, IRD, SESSTIM, Hop Sainte Marguerite, Department of Clinical Pharmacology, CAP-TV, Marseille, France.

Katrin Skala (K)

Department of Child and Adolescent Psychiatry, Medical University of Vienna, Austria.

Bo Söderpalm (B)

Laboratorio Farmaceutico CT, San Remo, Italy.

Lorenzo Somaini (L)

Addiction Treatment Center, Local Health Unit, ASL Biella, Italy.

Wolfgang H Sommer (WH)

Medical Faculty, Institute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.

Rainer Spanagel (R)

Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.

Gabriele A Vassallo (GA)

Department of Internal Medicine, Barone Lombardo Hospital, Canicattì, Italy.

Henriette Walter (H)

Santa Chiara University Hospital, University of Pisa, Italy.

Wim van den Brink (W)

Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

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