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

Denis  O’Mahony; 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 Vandaele; Eline 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

doi:10.1093/ageing/afaa072

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 journal › Article › peer-review

69 Citations (Scopus)

22 Downloads (Pure)

Abstract

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 language	English
Pages (from-to)	605-614
Number of pages	10
Journal	Age and Ageing
Volume	49
Issue number	4
Early online date	2 Jun 2020
DOIs	https://doi.org/10.1093/ageing/afaa072
Publication status	Published - 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.

Keywords

adverse drug reactions
older people
multi-morbidity
polypharmacy
prevention
STOPP/START criteria
Software
software
RISK-FACTORS
EVENTS
ADULTS
INPATIENTS
RIGHT TREATMENT CRITERIA
INTERVENTIONS
PHARMACIST
SCREENING TOOL
QUALITY-OF-LIFE
ELDERLY-PATIENTS
Adverse drug reactions
Prevention
Polypharmacy
Older people
Multi-morbidity

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10.1093/ageing/afaa072Licence: Unspecified

SENATOR_Trial_AgeandAgeing_AAM
This is a pre-copyedited, author-produced version of an article accepted for publication in Age and Ageing following peer review. The version of record O'Mahony etal. Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial, Age and Ageing, Volume 49, Issue 4, July 2020, Pages 605–614, is available online at: https://doi.org/10.1093/ageing/afaa072.
Accepted author manuscript, 274 KBLicence: Unspecified
Figure1_AAMAccepted author manuscript, 94 KBLicence: Unspecified
Figure2_AAMAccepted author manuscript, 82.1 KBLicence: Unspecified

Cite this

O’Mahony, D., Gudmundsson, A., Soiza, R. L., Petrovic, M., Jose Cruz-Jentoft, A., Cherubini, A., Fordham, R., Byrne, S., Dahly, D., Gallagher, P., Lavan, A., Curtin, D., Dalton, K., Cullinane, S., Flanagan, E., Shiely, F., Samuelsson, Ó., Sverrisdóttir, Á., Subbarayan, S., ... Eustace, J. (2020). Prevention of Adverse Drug Reactions in Hospitalized Older Patients with Multi-morbidity and Polypharmacy: the SENATOR randomized controlled clinical trial. Age and Ageing, 49(4), 605-614. https://doi.org/10.1093/ageing/afaa072

Prevention of Adverse Drug Reactions in Hospitalized Older Patients with Multi-morbidity and Polypharmacy: the SENATOR randomized controlled clinical trial. / O’Mahony, Denis (Corresponding Author); Gudmundsson, Adalsteinn ; Soiza, Roy L. et al.
In: Age and Ageing, Vol. 49, No. 4, 07.2020, p. 605-614.

Research output: Contribution to journal › Article › peer-review

O’Mahony, D, Gudmundsson, A, Soiza, RL, Petrovic, M, Jose Cruz-Jentoft, A, Cherubini, A, Fordham, R, Byrne, S, Dahly, D, Gallagher, P, Lavan, A, Curtin, D, Dalton, K, Cullinane, S, Flanagan, E, Shiely, F, Samuelsson, Ó, Sverrisdóttir, Á, Subbarayan, S, Vandaele, L, Meireson, E, Montero-Errasquín, B, Rexach-Cano, A, Correa-Pérez, A, Lozano-Montoya, I, Vélez-Díaz-Pallarés, M, Cerenzia, A, Corradi, S, Soledad Cotorruelo Ferreiro, M, Dimitri, F, Marinelli, P, Martelli, G, Fong Soe Khioe, R & Eustace, J 2020, 'Prevention of Adverse Drug Reactions in Hospitalized Older Patients with Multi-morbidity and Polypharmacy: the SENATOR randomized controlled clinical trial', Age and Ageing, vol. 49, no. 4, pp. 605-614. https://doi.org/10.1093/ageing/afaa072

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

abstract = "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.",

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author = "Denis O{\textquoteright}Mahony and Adalsteinn Gudmundsson and Soiza, {Roy L.} and Mirko Petrovic and {Jose Cruz-Jentoft}, Alfonso and Antonio Cherubini and Richard Fordham and Stephen Byrne and Darren Dahly and Paul Gallagher and Amanda Lavan and Denis Curtin and Kieran Dalton and Shane Cullinane and Evelyn Flanagan and Frances Shiely and {\'O}lafur Samuelsson and {\'A}str{\'o}s Sverrisd{\'o}ttir and Selvarani Subbarayan and Lore Vandaele and Eline Meireson and Beatriz Montero-Errasqu{\'i}n and Aurora Rexach-Cano and Andrea Correa-P{\'e}rez and Isabel Lozano-Montoya and Manuel V{\'e}lez-D{\'i}az-Pallar{\'e}s and Annarita Cerenzia and Samanta Corradi and {Soledad Cotorruelo Ferreiro}, Maria and Federica Dimitri and Paolo Marinelli and Gaia Martelli and {Fong Soe Khioe}, Rebekah and Joseph Eustace",

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 Ram{\'o}n 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{\textquoteright}Regan, Aoife Harvey, Ruben Keane, M{\'a}ire McCarthy, Sarah O{\textquoteright}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{\textquoteright}Keeffe (chairperson), Prof. Liam Plant and Robin Webster (older person advocate). Funding: This work was supported by the European Commission{\textquoteright}s Seventh Framework Programme (FP7/2007– 2013) (grant number 305930) as part of the SENATOR project.",

year = "2020",

month = jul,

doi = "10.1093/ageing/afaa072",

language = "English",

volume = "49",

pages = "605--614",

journal = "Age and Ageing",

issn = "0002-0729",

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TY - JOUR

T1 - Prevention of Adverse Drug Reactions in Hospitalized Older Patients with Multi-morbidity and Polypharmacy

T2 - the SENATOR randomized controlled clinical trial

AU - O’Mahony, Denis

AU - Gudmundsson, Adalsteinn

AU - Soiza, Roy L.

AU - Petrovic, Mirko

AU - Jose Cruz-Jentoft, Alfonso

AU - Cherubini, Antonio

AU - Fordham, Richard

AU - Byrne, Stephen

AU - Dahly, Darren

AU - Gallagher, Paul

AU - Lavan, Amanda

AU - Curtin, Denis

AU - Dalton, Kieran

AU - Cullinane, Shane

AU - Flanagan, Evelyn

AU - Shiely, Frances

AU - Samuelsson, Ólafur

AU - Sverrisdóttir, Ástrós

AU - Subbarayan, Selvarani

AU - Vandaele, Lore

AU - Meireson, Eline

AU - Montero-Errasquín, Beatriz

AU - Rexach-Cano, Aurora

AU - Correa-Pérez, Andrea

AU - Lozano-Montoya, Isabel

AU - Vélez-Díaz-Pallarés, Manuel

AU - Cerenzia, Annarita

AU - Corradi, Samanta

AU - Soledad Cotorruelo Ferreiro, Maria

AU - Dimitri, Federica

AU - Marinelli, Paolo

AU - Martelli, Gaia

AU - Fong Soe Khioe, Rebekah

AU - Eustace, Joseph

N1 - 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.

PY - 2020/7

Y1 - 2020/7

N2 - 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.

AB - 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.

KW - adverse drug reactions

KW - older people

KW - multi-morbidity

KW - polypharmacy

KW - prevention

KW - STOPP/START criteria

KW - Software

KW - software

KW - RISK-FACTORS

KW - EVENTS

KW - ADULTS

KW - INPATIENTS

KW - RIGHT TREATMENT CRITERIA

KW - INTERVENTIONS

KW - PHARMACIST

KW - SCREENING TOOL

KW - QUALITY-OF-LIFE

KW - ELDERLY-PATIENTS

KW - Adverse drug reactions

KW - Prevention

KW - Polypharmacy

KW - Older people

KW - Multi-morbidity

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U2 - 10.1093/ageing/afaa072

DO - 10.1093/ageing/afaa072

M3 - Article

SN - 0002-0729

VL - 49

SP - 605

EP - 614

JO - Age and Ageing

JF - Age and Ageing

IS - 4

ER -

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

Abstract

Bibliographical note

Keywords

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Roy Soiza

Cite this

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

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Profiles

Roy Soiza

Cite this