. Author manuscript; available in PMC: 2016 Dec 17.

Published in final edited form as: Lancet. 2016 Nov 16;388(10062):2873–2884. doi: 10.1016/S0140-6736(16)31275-2

Table 2.

Efficacy analyses for primary and secondary outcomes using primary analysis with the stratification covariates as additive terms in the model

	Baseline	Control 4 mg LMTM twice a day change from baseline (n=348)	Treatment effects		Covariate effects

			75 mg LMTM twice a day (n=257)	125 mg LMTM twice a day (n=250)	Severity (mild)	Taking LMTM as monotherapy
ADAS-Cog	27·15 (26·09–28·21)	6·32 (5·31–7·34)	−0·02 (−1·60 to 1·56); p=0·9834	−0·43 (−2·06 to1·20); p=0·9323	−1·03 (−1·57 to −0·49); p=0·0009	−2·30 (−3·35 to −1·25); p<0·0001

ADCS-ADL	55·91 (54·58–57·24)	−8·22 (−9·63 to −6·82)	−0·93 (−3·12 to 1·26); p=0·8659	−0·34 (−2·61 to 1·93); p=0·9479	1·62 (1·02–2·23); p<0·0001	2·00 (0·65–3·35); p=0·0174

Lateral ventricular volume (cm³)	52·40 (49·93–54·87)	7·18 (6·63–7·74)	−0·60 (−1·47 to 0·27); p=0·6049	−0·58 (−1·46 to 0·31); p=0·6049	−0·12 (−0·25 to 0·01); p=0·3490	−0·13 (−0·42 to −0·16); p=0·6158

ADCS-CGIC		−1·03 (–1·16 to −0·90)	−0·06 (−0·27 to 0·14); p=0·7866	0·01 (−0·21 to 0·22); p=0·9504	0·16 (0·09–0·23); p<0·0001	0·42 (0·27–0·57); p<0·0001

MMSE	18·60 (18·24–18·96)	−3·73 (−4·23 to −3·23)	0·06 (−0·71 to 0·84); p=0·9997	0·50 (− 0·29 to 1·30); p=0·6888	0·03 (−0·51 to 0·56); p=0·9997	1·95 (1·24–2·66); p<0·0001

Data are mean (95% CI); p value. The effect for geographic regions is not shown because it was not significant for any of the outcomes. LMTM=leuco-methylthioninium bis(hydromethanesulfonate). Treatment effects are differences with respect to control change from baseline at 65 weeks. Estimates for the covariates severity and use of Alzheimer’s disease-labelled treatments are shown. Population weights are used for all covariates in the mixed model repeated measures analysis, except for the Alzheimer’s disease treatment term where the contrast was set to taking approved Alzheimer’s disease treatments. ADAS-Cog=Alzheimer’s Disease Assessment Scale-Cognitive Subscale. ADCS-ADL=Alzheimer’s Disease Co-operative Study-Activities of Daily Living. ADCS-CGIC=Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change scale. MMSE=Mini-Mental State Examination.