Topical glyceryl trinitrate (GTN) and eccentric exercises in the treatment of mid-portion achilles tendinopathy (the NEAT trial): a randomised double-blind placebo-controlled trial

PainSci » bibliography » Kirwan et al 2024
updated Nov 29, 2024

Tags: treatment, Achilles tendinitis

Two pages on PainSci cite Kirwan 2024: 1. The Complete Guide to Chronic Tension Headaches 2. Achilles Tendinitis Treatment Science

PainSci commentary on Kirwan 2024: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.

Kirwan et al tested topical nitro in a few dozen Irish folks at a Dublin hospital. They compared nitro to an “aqueous cream, which contained no ingredients that would aid in tendon recovery.” (And yet I can so easily imagine some crank arguing that tendons need to be hydrated. Easily.)

Everyone also did the same exercise program for six months: the Alfredson protocol (predictably), a bunch of calf exercise made fiddly by doing them the eccentric way (loaded elongation). “It is known” that the Alfredson protocol is no better than simpler weighlifting. The authors reference that evidence from 2015, explaining that it was “published after this trial was designed” … so this trial took at least a decade to pull off? Wowsers.

All that exercise, plus time, means that everyone was likely to get better, and they did. But did nitro-smeared heels heal faster?

The answer was … no difference. An utterly negative result on its face. Nitro conveyed no advantage whatsoever. It did convey some headaches though — a well-known side effect.

A line graph showing the progression of VISA-A scores (0–100) for two groups, GTN (blue) and Placebo (red), measured at four time points: Baseline, Week 6, Week 12, and Week 24. Both groups show an upward trend, indicating improvement over time. At Week 6, the Placebo group has slightly higher scores, but by Week 24, both groups converge to nearly identical scores. Error bars are included at each point, reflecting variability in the data. The graph title reads “Mean VISA-A Scores at each timepoint.” The x-axis represents timepoints, and the y-axis represents VISA-A scores.

Figure 3, Kirwan et al. 2024, British Journal of Sports Medicine

That is about as simple and clear as a graph of trial results can get! Even where the GTN and the placebo differ, the gap is much smaller than the error bars. Just absolutely no difference.

~ Paul Ingraham

original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

OBJECTIVES: To investigate if daily treatment with glyceryl trinitrate (GTN) ointment, over 24 weeks combined with a 12-week eccentric exercise programme is more effective for chronic mid-portion Achilles tendinopathy than placebo ointment and eccentric exercise.

METHODS: This was a single-site randomised double-blind placebo-controlled trial at an acute hospital, Dublin, Ireland. Patients with chronic mid-portion Achilles tendinopathy were randomised to either 24 weeks of daily GTN ointment or placebo ointment. Both groups received an identical 12-week eccentric exercise programme. The primary outcome measure was the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire at 24 weeks, which measures pain, function and activity. Secondary outcomes included pain severity, self-reported physical function, calf muscle function, pressure pain thresholds and ultrasound changes. Statistical analyses were performed according to intention-to-treat principles.

RESULTS: 76 patients (30 women; 46 men, mean age±SD, 45.6±8.2 years) were recruited for the trial. Significant improvements in VISA-A scores occurred in both groups at 6-week, 12-week and 24-week follow-up. The increase was not significantly different between groups, adjusted mean between-group difference from baseline to week 6, -1.33 (95% CI -6.96 to 4.31); week 12, -1.25 (95% CI -8.0 to 5.49) and week 24, -3.8 (95% CI -10.6 to 3.0); negative values favour GTN. There was no significant between-group difference in any of the secondary outcome measures at 6, 12 and 24 weeks.

CONCLUSIONS: Adding daily GTN ointment over 24 weeks to a 12-week eccentric exercise programme did not improve pain, function and activity level in patients with chronic mid-portion Achilles tendinopathy when compared with placebo ointment.

original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

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