Eight RCTs were included in the review with 2,433 participants.
In the pilot study, statistically significant results were reported, in which patients treated with propentofylline did better, compared with those on placebo in respect of the measures of metabolic function. For the neuropsychological measures, the MMSE and DSST showed a trend improvement for those on propentofylline versus placebo which was not statistically significant, whilst the fragmented picture test showed a statistically significant improvement (p<0.05). The second study (a Phase II study) found that the GBS and MMSE scores improved over three months for both treatment and placebo groups but the improvement was greater in the propentofylline group. The difference in improvement in GBS score ranged between 4 and 16 for different MMSE sub-groups on a scale of 156. The difference in improvement in MMSE was 1.3 on a scale of 30. Both these differences were statistically significant, but modest, and the clinical relevance is very doubtful. No benefits in terms of the psychometric assessments between the two groups were found and, thus, the efficacy of propentofylline as defined a priori was not demonstrated. In the RCT and 2 meta-analyses, the results are reported under the outcomes of global function, cognitive function, activities of daily living, and adverse events. Global function showed a slight improvement between baseline and 12 months for the propentofylline group and a decline for the placebo group over the same period. The difference in mean change from baseline was statistically significantly in the RCT and 1 meta- analysis. The treatment group showed greater improvement in condition at all points using the CGI score and the RCT (using the CGI score) reported a clinically relevant difference of -0.9 (plus/minus 1.1) at 12 months, but this was not statistically significant. Cognitive function (using mean SKT score) in the RCT showed an improvement for both groups at 3 months. The improvement was maintained in the propentofylline group at 12 months but the placebo group declined to baseline levels. The difference in mean change from baseline at 12 months was statistically significant in both the RCT (-1.4 plus/minus 1.0) and the meta-analysis (-0.8 plus/minus 0.5) In the RCT the mean total MMSE score for the propentofyllline group showed an improvement between baseline and 12 months, and the placebo group showed a decline in condition over the same period. The difference in mean change from baseline was statistically significant in both the RCT (1.2 plus/minus 1.1) and the meta-analysis (0.7 plus/minus 0.5). In activities of Daily Living, the mean total NAB score from the RCT for both treatment groups showed a decline in condition throughout the course of the study, but was greater in the placebo group. The difference in mean change from baseline was statistically significant in both the RCT (-1.2 plus/minus 1.0) and the meta-analysis (-0.4 plus/minus 0.4). Adverse events reported were similar to those with the use of donepezil with 40% reported for the intervention group and 22% in the placebo group. Specific adverse events reported were: 1. Nausea (10% versus 4% in the placebo group). 2. Dizziness (9% versus 4% in the placebo group);. 3. Headache (7% versus 3% in the placebo group). 4. Gastrointestinal pain (5% versus 2% in the placebo group).