Integrated care pathways (ICPs) combine structured, multidisciplinary care plans that coordinate specialties, investigations, treatments and rehabilitation. ICPs are used for a range of long-term conditions and have been proposed as a scalable approach to manage the heterogeneous, multisystem problems seen in Long COVID (LC). The STIMULATE-ICP trial was designed to evaluate whether adding specific diagnostic and rehabilitation components to specialist LC clinic care improves patient-reported outcomes, with particular focus on fatigue.
STIMULATE-ICP was a phase 3, cluster-randomized, multicenter trial conducted in six National Health Service (NHS) specialist LC clinics in England. Clusters were defined at the primary care network (PCN) level and randomized to deliver one of four standard-of-care allocations in their area. Adults aged ≥18 years with LC — defined by the trial as persistent, otherwise unexplained post-COVID symptoms for ≥4 weeks (a prior positive SARS‑CoV‑2 test was not required) — were eligible at first referral to one of the six clinics. The trial ran from the first enrolment on 22 August 2022 to the last on 7 August 2024.
The trial compared four allocations delivered as local standard of care:
Cluster allocation included 122 PCN clusters: 33 allocated to Coverscan, 32 to digital rehabilitation, 27 to both interventions, and 30 to neither.
From 6,934 screened individuals, 1,152 adults consented for data use in the ICP trial and were allocated according to their PCN’s randomization. Allocation counts by individual were: Coverscan n = 288, digital rehabilitation n = 258, both n = 302, and neither (usual care) n = 304. Baseline mean Fatigue Assessment Scale (FAS) score across participants was 35.8 (s.d. 8.21). Two-thirds of participants were female (66.4%).
The primary outcome was mean Fatigue Assessment Scale (FAS) at 12 weeks. Secondary endpoints included FAS at 24 weeks and patient-reported health status measured by the EQ-5D-5L visual assessment scale at 12 and 24 weeks.
Across all trial arms, participants experienced improved fatigue by 12 weeks: the overall mean FAS fell by 4.5 points to 31.3 (s.d. 9.31). Compared with the usual care (neither) allocation, the estimated effects on 12-week FAS were small and not statistically significant:
Absolute differences in secondary outcomes between intervention allocations and usual care were described as modest. Detailed secondary outcome data and subgroup analyses are reported in the trial’s supplementary information (pp. 1–121) referenced by the investigators.
No serious adverse events related to the ICP interventions (Coverscan or the digital rehabilitation platform) were reported in the source article summary.
The STIMULATE-ICP trial indicates that multidisciplinary, holistic clinical care delivered in specialist LC clinics is associated with reductions in fatigue over 12 weeks irrespective of the routine use of multi-organ MRI. The additions tested — Coverscan and the Living With COVID Recovery digital rehabilitation platform — did not show statistically significant incremental benefits on the 12-week FAS compared with usual care in this cluster-randomized setting, although the authors note digital rehabilitation could have utility in longer-term LC management.
The trial demonstrates feasibility of large, multi-site, cluster-randomized evaluations of ICP components for LC. The investigators conclude that further, larger trials are required to define optimal ICP elements and to clarify longer-term clinical benefits, and they provide an ISRCTN identifier for the platform trial: ISRCTN10665760.