Stimulated by Liu et al 2020.[1]
Diagram by MC.
EA – electroacupuncture
key to acronyms
SCC – severe chronic constipation
IF – impact factor
CSBM – complete spontaneous bowel movement
5–HT4 – 5–hydroxytryptamine 4 receptor
This paper came out in December 2020, and I have been sitting on it ever since waiting for the urge to blog about it.
It is a big non-inferiority trial (n=560) that follows on from the huge sham controlled trial (n=1075) I highlighted previously on the blog: EA for chronic severe functional constipation.[2] The big sham controlled trial was published in Annals of Internal Medicine (IF 11.75) and this non-inferiority trial just popped up in the American Journal of Gastroenterology (IF 6.73).
I think the populations are the same, since despite the condition label having changed a little, the actual inclusion criteria are almost identical. The primary outcome was again CSBMs per week, and in both these trials the baseline means are around 0.5, so that is 1 proper bowel movement per fortnight.
Prucalopride is a high affinity 5–HT4 agonist
Prucalopride is a high affinity 5–HT4 agonist with potent effects on bowel motility, and is currently the most effective treatment available for SCC. However, it does come with some side-effects:[1]
nausea (13.6%)
diarrhoea (11.8%)
abdominal pain (13.7%)
headache (17.5%)
The EA protocol was performed in exactly the same way as in the previous sham controlled trial, and is described in the previous blog. In brief they used a pair of needles in the muscle of the abdominal wall on each side, and manual needling of ST37 on both sides. Additional points were available for severe straining (EA to BL33) and for symptoms of anxiety or depression (GV20 GV24 manual stimulation)
Perhaps the most striking aspect of the treatment protocol is that they managed to get 28 sessions completed in just 8 weeks. That was 5 per week for 2 weeks and 3 per week for the remaining 6 weeks.
The EA intensity quoted in the protocol is the same as in the previous trial, 0.1 to 1.0mA, which seems quite low intensity, but I note that in the 2016 publication they say:
preferably with skin around the acupoints shivering mildly without pain
The frequency setting is described as a dilatational wave 10/50Hz, which means that the device gradually ramps the frequency up and down between these to frequencies. This is quite different to the Han-style dense dispersed frequencies that change abruptly every 3 seconds from low to high and then back to low.
The results show prucalopride getting off to a good start with a mean of 2 CSBMs at week 1, whilst EA is lagging slightly at 1.5. But remember the baseline was 0.5, so that is a 3 to 4-fold improvement in a week. By the end of week 2 EA catches up with prucalopride, but that constitutes 10 sessions of acupuncture already. The outcome hovers between 2 and 2.5 for the rest of the trial: in total that is 32 weeks from the start of treatment.
I have to say that I was surprised to see the EA group continue on the same trajectory for the 6 months of follow up without further treatment, whilst the prucalopride group continued taking the drug for the whole time.
The non-inferiority was calculated based on a 10% difference in the proportion of patients with 3 or more CSBM per week over weeks 3 to 8. The results suggest equivalence of the interventions based on this 10% difference.
In terms of adverse events, the majority were haematomas in the EA group, and adding them all together came to a rate of nearly 18%. The prucalopride group had a rate of over 44%, mainly diarrhoea, abdominal pain and headache.
EA is of equivalent effectiveness to prucalopride
In summary this is a well-designed and conducted non-inferiority trial of EA against the best convention care for SCC that demonstrates an intense course of EA is of equivalent effectiveness, and lasts for at least 6 months after treatment with relatively few side-effects.
The current cost of prucalopride in the UK is just under £60 per month, which works out to a total cost of £480 for the length of this trial per patient (8 months).
References
1 Liu B, Wu J, Yan S, et al. Electroacupuncture vs Prucalopride for Severe Chronic Constipation. Am J Gastroenterol Published Online First: December 2020. doi:10.14309/ajg.0000000000001050
2 Liu Z, Yan S, Wu J, et al. Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial. Ann Intern Med 2016;165:761–9. doi:10.7326/M15-3118
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