Dataset Information

Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19).

ABSTRACT:

Objective

To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19.

Design

Multicentre, randomised, controlled, open-label trial.

Setting

9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021.

Participants

Adults hospitalised with COVID-19 and receiving oxygen therapy.

Intervention

Inhaled ciclesonide 320 µg two times a day for 14 days versus standard care.

Main outcome measures

Primary outcome was duration of oxygen therapy, an indicator of time to clinical improvement. Key secondary outcome was a composite of invasive mechanical ventilation/death.

Results

Data from 98 participants were analysed (48 receiving ciclesonide and 50 receiving standard care; median (IQR) age, 59.5 (49-67) years; 67 (68%) men). Median (IQR) duration of oxygen therapy was 5.5 (3-9) days in the ciclesonide group and 4 (2-7) days in the standard care group (HR for termination of oxygen therapy 0.73 (95% CI 0.47 to 1.11), with the upper 95% CI being compatible with a 10% relative reduction in oxygen therapy duration, corresponding to a <1 day absolute reduction in a post-hoc calculation). Three participants in each group died/received invasive mechanical ventilation (HR 0.90 (95% CI 0.15 to 5.32)). The trial was discontinued early due to slow enrolment.

Conclusions

In patients hospitalised with COVID-19 receiving oxygen therapy, this trial ruled out, with 0.95 confidence, a treatment effect of ciclesonide corresponding to more than a 1 day reduction in duration of oxygen therapy. Ciclesonide is unlikely to improve this outcome meaningfully.

Trial registration number

NCT04381364.

SUBMITTER: Brodin D

PROVIDER: S-EPMC9950582 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19).

Brodin Daniel D Tornhammar Per P Ueda Peter P Krifors Anders A Westerlund Eli E Athlin Simon S Wojt Sandra S Elvstam Olof O Neumann Anca A Elshani Arsim A Giesecke Julia J Edvardsson-Källkvist Jens J Bunpuckdee Sayam S Unge Christian C Larsson Martin M Johansson Björn B Ljungberg Johan J Lindell Jonas J Hansson Johan J Blennow Ola O Andersson Daniel Peter DP

BMJ open 20230222 2

<h4>Objective</h4>To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19.<h4>Design</h4>Multicentre, randomised, controlled, open-label trial.<h4>Setting</h4>9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021.<h4>Participants</h4>Adults hospitalised with COVID-19 and receiving oxygen therapy.<h4>Intervention</h4>Inhale ...[more]

PMID: 36813503

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Project description:BackgroundPatients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia.MethodsWe did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov, NCT04324073.Findings165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0-71·1] in the sarilumab group and 62·8 years [56·0-71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] -11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69-1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73).InterpretationSarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival.FundingAssistance publique-Hôpitaux de Paris.

Project description:ObjectivesTo assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness.MethodsCOVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here.ResultsThe analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms.DiscussionOur findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

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Dataset Information

Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19).

Objective

Design

Setting

Participants

Intervention

Main outcome measures

Results

Conclusions

Trial registration number

Publications

Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19).

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