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Randomized Controlled Trial
. 2025 Aug 1;53(8):e1542-e1553.
doi: 10.1097/CCM.0000000000006698. Epub 2025 May 22.

Improving Recovery and Outcomes Every Day After the ICU (IMPROVE): A Randomized Controlled Trial

Sikandar H Khan  1   2 , Anthony J Perkins  3 , Frederick W Unverzagt  4 , Sophia Wang  4 , Lyndsi R Moser  4 , Salwa Moiz  2 , Samreen Jawaid  2 , Dexter Corlett  5 , Daniel O Clark  2   5 , Malaz A Boustani  6 , Sujuan Gao  3 , Babar A Khan  1   2
Affiliations
Randomized Controlled Trial

Improving Recovery and Outcomes Every Day After the ICU (IMPROVE): A Randomized Controlled Trial

Sikandar H Khan et al. Crit Care Med. .

Abstract

Objectives: To investigate the effects of a 12-week, web-based, combined cognitive and physical training intervention on cognitive performance among ICU delirium survivors.

Design: Prospective, four-arm randomized controlled trial.

Setting: Four sites (academic, county, community ICUs).

Patients: ICU adults 50 years old or older with at least one instance of ICU delirium or subsyndromal delirium.

Interventions: Patients were randomized to one of four groups: physical exercise-cognitive training (PE-CT), physical exercise-cognitive control (PE-CC), stretching control-cognitive training (SC-CT), or stretching control-cognitive control (SC-CC).

Measurements and main results: The primary outcome was cognitive function at 3 and 6 months after start of intervention, as assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). One hundred fifty-three patients were randomized to either: PE-CT, n = 41; PE-CC, n = 41; SC-CT, n = 36; or SC-CC, n = 35. There was a significant difference on changes in RBANS z scores among the four arms (interaction term p = 0.012). The mean RBANS z scores ranged from -2.66 to +1.43 (change in RBANS z score of ± 0.5-0.6 may be clinically significant). The SC-CT group had statistically significant worsening in cognitive scores compared with the SC-CC group at 3 (mean estimated difference in change from baseline, -0.28; 95% CI, -0.53 to -0.02; p = 0.035) and 6 months (mean estimated difference in change from baseline, -0.29; 95% CI, -0.53 to -0.04; p = 0.021). Compared with the SC-CC group, the PE-CC group had statistically significant worsening in cognitive scores at 6 month (mean estimated difference in change from baseline, -0.26; 95% CI, -0.49 to -0.02; p = 0.035). There were no significant differences between groups in physical or mental quality of life, depression, or anxiety outcomes at any of the timepoints.

Conclusions: The Improving Recovery and Outcomes Every Day After the ICU (IMPROVE) trial did not result in improved cognitive, physical, mental health, or quality of life measures at 3 or 6 months. We found a drop in cognitive performance among patients receiving cognitive training from baseline to 3 months postintervention.

Trial registration: ClinicalTrials.gov NCT03095417.

Keywords: cognitive training; critical care; delirium; physical exercise; post-intensive care syndrome.

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Conflict of interest statement

Dr. S. H. Khan is supported by the National Institute on Aging (NIA) (K76 AG074925) Dr. B. A. Khan is supported by the NIA (R01 AG06763) and National Heart, Lung, and Blood Institute (R01 HL131730). Dr. Gao supported by the NIA (K07 AG076659, P30 AG010133, and P30 AG072976). Drs. S. H. Khan, Perkins, Unverzagt, Wang, Moser, Clark, Boustani, Gao, and B. A. Khan received support for article research from the National Institutes of Health (NIH). Drs. Perkin’s, Moser’s, and Clark’s institutions received funding from the NIA. Dr. Wang received funding from the American Psychiatric Publishing Institute and the NIA Data and Safety Monitoring Board head. Dr. Moser’s institution received funding from the National Institute on Minority Health and Health Disparity. Drs. Boustani’s and B. A. Khan’s institutions received funding from the NIH. Dr. Boustani received funding from Blue Agilis, DigiCare Realized, PPHM, LLC, RestUP, Lillly, Biogen, Genentech, and Merck. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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