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Clinical Trial
. 2024 Dec 24;28(1):9.
doi: 10.1007/s10456-024-09962-4.

Effect of oral nintedanib vs placebo on epistaxis in hereditary hemorrhagic telangiectasia: the EPICURE multicenter randomized double-blind trial

Ruben Hermann  1 , Vincent Grobost  2 , Xavier Le-Guillou  3 , Christian Lavigne  4 , Antoine Parrot  5 , Sophie Rivière  6   7 , Julie Séguier  8 , Anne-Emmanuelle Fargeton  9 , Aurélie de-Montigny  10 , Margaux Huot  10 , Evelyne Decullier  11 , Adeline Roux  11 , Caroline Gervaise  12 , César Cartier  13 , Xavier Dufour  14 , Margaux Grall  15 , Frank Jegoux  16 , Laurent Laccourreye  17 , Justin Michel  18 , Nicolas Saroul  19 , Isabelle Wagner  20 , Mallorie Kerjouan  21 , Sophie Dupuis-Girod  9
Affiliations
Clinical Trial

Effect of oral nintedanib vs placebo on epistaxis in hereditary hemorrhagic telangiectasia: the EPICURE multicenter randomized double-blind trial

Ruben Hermann et al. Angiogenesis. .

Abstract

Epistaxis greatly affects patients with hereditary hemorrhagic telangiectasia (HHT). Although few systemic treatment exist, nintedanib, is a good candidate thanks to its anti-angiogenic activity. Our main objective was to evaluate the efficacy of oral nintedanib on epistaxis duration in HHT patients with moderate to severe epistaxis. This multicenter phase 2 randomized, placebo-controlled, double-blind trial was conducted between June 2020 and February 2023. Inclusion criteria were being over 18 years old and having a confirmed HHT diagnosis with an epistaxis severity score greater than 4. Sixty patients were randomized to receive either nintedanib or placebo for 12 weeks with a 12 week follow-up. The primary endpoint was the proportion of patients achieving a reduction of at least 50% in mean monthly epistaxis duration comparing the 8 weeks before treatment to the last 8 weeks of treatment. Main secondary outcomes included monthly duration and frequency of epistaxis and hemoglobin levels. Of the 60 randomized patients, 56 completed the trial. Thirteen patients (43%) in the nintedanib group vs 8 (27%) in the placebo group met the primary endpoint (p = 0.28). We observed a significant decrease in median epistaxis (57% vs 27%, p = 0.013) and a significant increase in median hemoglobin levels (+ 18 vs - 1 g/L, p = 0.02) in the nintedanib vs the placebo group. Although we did not achieve our primary outcome, we observed a significant reduction in epistaxis duration and a significant increase in hemoglobin levels in patients treated with nintedanib. This supports the efficacy of nintedanib, and further studies are needed.

Keywords: Anemia; Anti-angiogenic; Epistaxis; Hereditary hemorrhagic telangiectasia; Nintedanib; Tyrosine kinase inhibitors.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram
Fig. 2
Fig. 2
Evolution of monthly epistaxis duration before during and after treatment. Median, 1st and 3rd quartile of epistaxis monthly duration before, during and after treatment in the nintedanib (blue) and placebo (dark grey) groups considering that 1 month is equal to 4 weeks i.e. 28 days. ITT population
See this image and copyright information in PMC

References

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