OBJECTIVES: To assess efficacy and safety of once-daily controlled-release (CR) formulation of pregabalin in patients with postherpetic neuralgia.
METHODS: An enriched enrollment, randomized withdrawal trial, with 6-week single-blind pregabalin treatment phase and 13-week double-blind phase, where patients with =50% decrease in mean pain score at single-blind end point from baseline were randomized (1:1) to pregabalin CR (82.5 to 660 mg/d) or placebo. Primary efficacy outcome was time to loss of therapeutic response (LTR) (<30% decrease in weekly mean pain score from single-blind baseline or discontinuation due to adverse event or lack of efficacy). Secondary efficacy outcomes included change in weekly mean pain score (1-wk recall period) at double-blind end point.
RESULTS: In total, 801 patients were randomized and treated in the single-blind phase, and 413 in the double-blind phase (208, pregabalin CR; 205, placebo). Pregabalin CR significantly increased time to LTR versus placebo (Kaplan-Meier analysis) with significantly fewer LTR events with pregabalin CR than with placebo (29 [13.9%] vs. 63 [30.7%]; P<0.0001). Median time to LTR was not estimable. Pregabalin CR significantly improved weekly mean pain score versus placebo: LS mean difference (95% CI) of -1.11 (-1.47, -0.75) and -1.00 (-1.34, -0.65) (P<0.0001) from single-blind baseline and double-blind baseline, respectively. Most commonly reported adverse events in the single-blind phase were dizziness, somnolence, and peripheral edema. Pregabalin CR was well tolerated.
DISCUSSION: Time to LTR was significantly longer with pregabalin CR than with placebo. Safety profile of pregabalin CR was comparable to that reported for the immediate-release formulation in patients with postherpetic neuralgia.
A study which demonstrate that pregabalin CR significantly reduces the number of LTR events in subjects with pain. I am not so convinced that the reported statistically significant increase of time to LTR events is really clinically significant (Figure 3).
Assuming a significant number of people on the med would have side effects in the first 6 weeks, would the absence of them once taking placebo lead to "unblinding"? Overall, there was a modest improvement in symptoms.
It's hard to follow this pharmaceutical sponsored study of a controlled release (and likely more expensive than generic) pregabalin for post herpetic neuralgia. Almost half the initial group did not respond. Responders were randomized to continuing it, or switching to placebo. Most of the placebo patients continued to feel better, but more of the ongoing pregabalin treatment patients did. I can't see this changing my approach.
The topic of the study appeals as being attractive. If I had only time to read the abstract, I would not get the point. If the authors claim that time to LTS was different, then there should be a reference to time in the abstract. If I had to transmit the general results of the study to a patient, I could not describe this feature. Table 2 is an important piece of evidence because it shows the important heterogeneity of the population and the parameters being analysed. This can be recognized quite easily since, in some situations, the SD is larger or quite close to the mean. It has to be due to this statistical "malheur" that the authors did not depict any measures of variation, i.e. SD, in Figure 4. It is astonishing that a Journal and its Editors go on to publish such studies.
We should be aware that this is a randomized clinical trial sponsored by a drug company. That means that we need to scrutinize every detail of the paper. 1) Why the researchers compared with placebo instead with non-CR pregabalin? 2) What does it really mean time to loss therapeutic response in the clinical setting? 3) Is it clinically relevant a difference of less than 1 point in a 10-point pain scale between groups?