Medical hypnosis versus structured relaxation as adjunct to pulmonary rehabilitation for anxiety in chronic obstructive pulmonary disease (HYPNOBPCO_2): a cluster-randomised, active-comparator trial

Background: Anxiety affects 22-56% of patients with COPD. It is independently associated with increased exacerbations, readmissions, and mortality. Medical hypnosis transiently alleviates state anxiety in severe COPD, and attenuates experimentally-induced dyspnoea in healthy volunteers. We aimed to assess the efficacy of hypnosis as adjunct therapy for anxiety during Pulmonary Rehabilitation (PR) versus an active comparator controlling for general motivation and relaxation. Methods. HYPNOBPCO_2 was a single-centre, phase 2, cluster-randomised, active-comparator, parallel-group, superiority trial done at Centre Hospitalier de Bligny, France. Adults +30 years with established COPD, mMRC dyspnoea grade +2, and +10 pack-years were eligible. Consecutive pulmonary rehabilitation cohorts (clusters) were randomly assigned (1:1) to medical hypnosis or structured relaxation, both adjunctive to a 4-week inpatient PR. The primary outcome was the six-item State-Trait Anxiety Inventory (STAI-6) at week 4, analysed in the intention-to-treat population. Secondary outcomes were sensory and affective dyspnoea (Multidimensional Dyspnea Profile sensory and affective sub-scales, COPD Assessment Test) and functional capacity (6-minute walk distance). A moderation analysis tested whether the hypnosis effect varied with baseline sensory and affective dyspnoea burden using Bayesian inference. This trial was registered prospectively (NCT04868357) and the protocol published. Findings. Between 27/09/2021 and 31/01/2024, 79 participants in 24 clusters were randomised (medical hypnosis n = 36, age 64.9 [8.3], 20 female; relaxation n = 43, age 67.4 [9.1], 23 female). Anxiety improved in both arms (deltaSTAI-6 = -5.72, posterior probability of reduction beyond MCID = 0.93). Medical hypnosis did not show an advantage over relaxation overall (deltaSTAI-6 = 0.95; posterior probability of reduction beyond MCID = 0.12). Medical hypnosis did show an advantage that scaled with baseline dyspnoea profile: in patients with high sensory and low affective burden, the predicted anxiety reduction relative to relaxation was larger and more probable (deltaSTAI-6 = -9.26; posterior probability of reduction beyond the 3-point MCID = 0.81). No clinically important safety issues were associated with either intervention and there were no deaths. Interpretation. Anxiety improved under both adjunctive mind-body interventions. The usefulness of hypnosis beyond relaxation was predicted by baseline dyspnoea profile, concentrating in patients with predominantly sensory burden. Future trials should focus on evaluating complementary interventions against burden phenotypes, ultimately paving the way for personalized interventions. Funding. Helebor Foundation; Agence Nationale de la Recherche.