Nijasri C Suwanwela1, Christopher L H Chen2, Chun Fan Lee3, Sherry H Young4, San San Tay4, Thirugnanam Umapathi5, Annabelle Y Lao6, Herminigildo H Gan7, Alejandro C Baroque Ii8, Jose C Navarro9, Hui Meng Chang10, Joel M Advincula11, Sombat Muengtaweepongsa12, Bernard P L Chan13, Carlos L Chua14, Nirmala Wijekoon15, H Asita de Silva16, John Harold B Hiyadan17, Ka Sing Lawrence Wong18, Niphon Poungvarin19, Gaik Bee Eow20, Narayanaswamy Venketasubramanian21. 1. Chulalongkorn University, Chulalongkorn Stroke Centre, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. 2. Memory Aging and Cognition Centre, Department of Pharmacology, National University of Singapore, Singapore, Singapore. 3. School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong. 4. Changi General Hospital, Singapore, Singapore. 5. National Neuroscience Institute, Tan Tock Seng Hospital Campus, Singapore, Singapore. 6. Southern Philippines Medical Center, Davao, Philippines. 7. Jose Reyes Memorial Medical Center, San Lazaro Compound, Manila, Philippines. 8. University of Santo Tomas Hospita, Manila, Philippines. 9. Jose R Reyes Medical Center, Neuroscience Institute St Luke's Medical Center, University of Santo Tomas Hospital, Manila, Philippines. 10. National Neuroscience Institute, Singapore General Hospital Campus, Singapore, Singapore. 11. West Visayas State University Medical Center, Iloilo, Philippines. 12. Thammasat University, Pathum Thani, Thailand. 13. National University Hospital, National University Health System, Singapore, Singapore. 14. Philippine General Hospital, University of the Philippines, Manila, Philippines. 15. University of Kelaniya, Annasihena Road, Ragama, Sri Lanka. 16. Clinical Trials Unit, Faculty of Medicine, University of Kelaniya, Annasihena Road, Ragama, Sri Lanka. 17. Baguio General Hospital and Medical Centre, Baguio, Philippines. 18. Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. 19. Siriraj Hospital, Bangkoknoi, Bangkok, Thailand. 20. Penang Hospital, Jalan Residensi, George Town, Malaysia. 21. Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
Abstract
BACKGROUND AND PURPOSE:MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. METHODS: Data from the CHInese MedicineNeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. RESULTS: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0-1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. CONCLUSIONS: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.
RCT Entities:
BACKGROUND AND PURPOSE: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. METHODS: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. RESULTS: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0-1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. CONCLUSIONS: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.
Authors: H Quintard; M Borsotto; J Veyssiere; C Gandin; F Labbal; C Widmann; M Lazdunski; C Heurteaux Journal: Neuropharmacology Date: 2011-05-14 Impact factor: 5.250
Authors: C Heurteaux; C Widmann; H Moha ou Maati; H Quintard; C Gandin; M Borsotto; J Veyssiere; B Onteniente; M Lazdunski Journal: Cerebrovasc Dis Date: 2013-03-14 Impact factor: 2.762
Authors: Christopher L H Chen; Sherry H Y Young; Herminigildo H Gan; Rajinder Singh; Annabelle Y Lao; Alejandro C Baroque; Hui Meng Chang; John Harold B Hiyadan; Carlos L Chua; Joel M Advincula; Sombat Muengtaweepongsa; Bernard P L Chan; H Asita de Silva; Somchai Towanabut; Nijasri C Suwanwela; Niphon Poungvarin; Siwaporn Chankrachang; K S Lawrence Wong; Gaik Bee Eow; Jose C Navarro; Narayanaswamy Venketasubramanian; Chun Fan Lee; Marie-Germaine Bousser Journal: Stroke Date: 2013-06-18 Impact factor: 7.914
Authors: Simić-Panić S Dušica; Gordana V Devečerski; Mirjana N Jovićević; Nedeljko M Platiša Journal: Ann Indian Acad Neurol Date: 2015 Oct-Dec Impact factor: 1.383