Prevention of Adverse Drug Reactions in Hospitalized Older Patients with Multi-morbidity and Polypharmacy: the SENATOR randomized controlled clinical trial

Denis O’Mahony* (Corresponding Author), Adalsteinn Gudmundsson, Roy L. Soiza, Mirko Petrovic, Alfonso Jose Cruz-Jentoft, Antonio Cherubini, Richard Fordham, Stephen Byrne, Darren Dahly, Paul Gallagher, Amanda Lavan, Denis Curtin, Kieran Dalton, Shane Cullinane, Evelyn Flanagan, Frances Shiely, Ólafur Samuelsson, Ástrós Sverrisdóttir, Selvarani Subbarayan, Lore VandaeleEline Meireson, Beatriz Montero-Errasquín, Aurora Rexach-Cano, Andrea Correa-Pérez, Isabel Lozano-Montoya, Manuel Vélez-Díaz-Pallarés, Annarita Cerenzia, Samanta Corradi, Maria Soledad Cotorruelo Ferreiro, Federica Dimitri, Paolo Marinelli, Gaia Martelli, Rebekah Fong Soe Khioe, Joseph Eustace

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Background: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention.

Methods: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n= 772, mean number of daily medications= 9.34) or standard care alone (control, n= 765, mean number of daily medications= 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life.

Results: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (similar to 15%).

Conclusions: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

Original languageEnglish
Pages (from-to)605-614
Number of pages10
JournalAge and Ageing
Issue number4
Early online date2 Jun 2020
Publication statusPublished - Jul 2020

Bibliographical note

Acknowledgements: The trial was co-ordinated and the trial database was managed by the staff of the Health Research Board Clinical Research Facilities at University College Cork (HRB CRF-C). The authors wish to thank the patients and staff of the participating hospitals for their cooperation: (i) Cork University Hospital, Cork, Ireland. (ii) Ghent University Hospital, Ghent, Belgium. (iii)
Hospital Universitario Ramón y Cajal, Madrid, Spain. (iv) Ospedali Riuniti, Ancona, Italy. (v) Landspitali University Hospital, Reykjavik, Iceland. (vi) Aberdeen Royal Infirmary, Aberdeen, Scotland. The authors wish to acknowledge the
contributions of the staff of the following organizations in the SENATOR trial: (i) ClinInfo S.A, Lyons, France (Philippe Foerster). (ii) ARTTIC International Management Services, Munich, Germany (Dr Otilia Postea). (iii) Clanwilliam Health, Dublin, Ireland (Joseph McMullin, Anthony Maguire). (iv) HRB Clinical Research Facility— Cork, Cork, Ireland (Mary-Claire O’Regan, Aoife Harvey,
Ruben Keane, Máire McCarthy, Sarah O’Meara). The authors further wish to acknowledge the oversight of the external Scientific Advisory Board (SAB) and the Ethics and Safety Review Group (ESRG) during the conduct of the SENATOR trial. SAB members included: Prof. Cillian Twomey (chairperson), Prof. Peter Crome, Dr Paul Jansen, Prof. Anne Spinewine, Prof. Jamie Coleman, Prof. Tischa van der Cammen and Prof. Jose M. Ribera-Casado. ESRG members included Prof. Shaun O’Keeffe (chairperson), Prof. Liam Plant and Robin Webster (older person advocate).

Funding: This work was supported by the European Commission’s Seventh Framework Programme (FP7/2007– 2013) (grant number 305930) as part of the SENATOR project.


  • adverse drug reactions
  • older people
  • multi-morbidity
  • polypharmacy
  • prevention
  • STOPP/START criteria
  • Software
  • software
  • Adverse drug reactions
  • Prevention
  • Polypharmacy
  • Older people
  • Multi-morbidity


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