Long COVID Infections and Infestations
Conditions
Interventions
Tocilizumab/placebo subcutaneously for 12 weeks
Dosage: 162 mg subcutaneous injection.
Frequency of administration: body weight 20 mg/L)
4. Participation in the MRI sub-study (Yes/No)
5. Acute admiss
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Age =18 years old and =80 years old 2. Clinical diagnosis of COVID-19 at least 3 months prior to consent. Patient-reported positive test is acceptable 3. Patient does not feel fully recovered at recruitment after COVID-19 (response no or unsure to “do you feel fully recovered from your COVID-19”) 4. CRP >5 mg/L persistently raised after contracting COVID-19 and prior to randomisation 5. Euroqol EQ5D-5L utility index =0.90 units prior to randomisation 6. Reasonable understanding of the English language assessed by the research team (i.e. able to understand the risks of taking part in the trial and complete the measurements including the patient-reported outcome measures)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 16/01/2025: 1. Other comorbidity indicating survival at one year from consent is unlikely 2. Active malignancy or on treatment for malignancy 3. Unable or unwilling to provide written consent 4. Inability to comply with protocol-directed procedures and assessments 5. Current immunosuppression therapy including oral corticosteroids 6. Prior use of the trial drug within 3 months of consent (including intra-venous Tocilizumab for acute COVID). 3 months is five-half lives of tocilizumab 7. Involvement in other trials involving an IMP either concurrently or within four months of consent - to allow washout. This includes medications prescribed for acute COVID studies. 8. Previous adverse event to tocilizumab, either a severe allergic reaction or deranged liver function tests 9. Hepatic transaminases greater than three times the upper limit of normal 10. Low neutrophil (below 2 x 109/L) or low platelet levels (below 100 x 10e3/µL) 11. Signs of active infection 12. Receipt of live vaccine within 3 months or planning a live vaccine during the trial period. Most COVID vaccines are not live. 13. Pregnancy or breastfeeding, or planning a pregnancy during the trial period or unable or unwilling to meet the contraception criteria (see below) 14. Latent TB: to be excluded with IGRA testing and if positive exclude and refer for treatment as per national guidelines. 15. New diagnosis or on treatment for HIV 16. Past history of diverticulitis 17. Significant alcohol or substance misuse 18. History of clinically significant hypersensitivity reaction or significantly deranged liver function tests with other medication 19. Hepatitis B 20. Exclude Hepatitis C if untreated: on testing antibody positive and detectable viral load. If antibody positive, but viral load negative compatible with previous infection only participant can be included. 21. Supervised exercise rehabilitation programme including exercise training, or other rehabilitation therapy for example fatigue management or breathing retraining lasting for a minimum of 4 sessions within three months of consent or planned to occur during the trial period 22. New medication for Long Covid symptoms started within six weeks of consent 23. No new weight management medication to start within three months of consent or during the trial period, for example glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors _____ Previous exclusion criteria: 1. Other comorbidity indicating survival at one year from consent is unlikely 2. Active malignancy or on treatment for malignancy 3. Unable or unwilling to provide written consent 4. Inability to comply with protocol-directed procedures and assessments 5. Current immunosuppression therapy including oral corticosteroids 6. Prior use of the trial drug within 3 months of consent (including intra-venous Tocilizumab for acute COVID). 3 months is five-half lives of tocilizumab 7. Involvement in other trials involving an IMP either concurrently or within four months of consent - to allow washout. This includes medications prescribed for acute COVID studies. 8. Previous adverse event to tocilizumab, either a severe allergic reaction or deranged liver function tests 9. Hepatic transaminases greater than three times the upper limit of normal 10. Low neutrophil (below 2 x 109/L) or low platelet levels (below 100 x 10e3/µL) 11. Signs of active infection 12. Receipt of live vaccine within 3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Health-related quality of life measured using Euroqol five-dimension five-level questionnaire – utility index assessed at baseline, after 12 weeks (+2 weeks) of IMP/Placebo and after a further 12 weeks (+2 weeks) after the end of the intervention period | — |
Secondary
| Measure | Time frame |
|---|---|
| Current key secondary outcomes: Measured at baseline, after 12 weeks (+ 2 weeks) of IMP/Placebo and after a further 12 weeks (+2 weeks) after the end of the intervention period: 1. Symptoms measured using Symptom Questionnaires – fatigue and breathlessness (FACIT-Fatigue and Dyspnoea-12) 2. General and respiratory disease-specific health-related quality of health measured using EQ5D-5L Visual Analog Scale, St George’s Respiratory Questionnaire (SGRQ) and COVID-19 Yorkshire Rehabilitation Scale – modified version (C19YRSm) 3. Mental health measured using anxiety and depression questionnaires GAD-7 and PHQ-9 4. Physical performance measured using the Incremental Shuttle Walking Test, the Short Physical Performance Battery (SPPB) and hand grip strength 5. Daily physical activity measured using an accelerometer worn for 14 days 6. Cognitive impairment measured using Montreal Cognitive Assessment (MoCA) 7. Multi-organ function measured using blood biomarker levels (including full blood count, natriuretic peptides, kidney and liver function) and spirometry. 8. Systemic inflammation measured using a blood test for C-reactive protein 9. Frailty and activities of daily living measured using Fried’s frailty criteria and Nottingham Activities of Daily Living Scale, respectively Exploratory outcomes: Respiratory health substudy: Pulmonary pathophysiology assessed by CT thorax and full pulmonary function tests at baseline and after 12 weeks (+4 weeks) after IMP/Placebo: 1. Pulmonary pathology on CT thoracic imaging such as ground-glass opacities, interstitial abnormalities, established pulmonary fibrosis, or small airways disease suggestive of ongoing post-COVID pulmonary changes 2. Pulmonary function tests include spirometry, transfer factor, residual volume and total lung capacity Multi-organ health substudy: MRI markers of multi-organ inflammation evaluated by describing the presence or absence of multiorgan abnormality (defined as MRI abnormalities involving two or more or | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed