Prednisolone for loss of smell after COVID-19 infection
| ISRCTN | ISRCTN70794078 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN70794078 |
| EudraCT/CTIS number | 2021-004021-71 |
- Submission date
- 28/07/2021
- Registration date
- 09/06/2022
- Last edited
- 18/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Loss of the sense of smell (anosmia) is common in COVID-19 infections. Most patients regain a normal sense of smell within 4 weeks, but in 6-8% the sense of smell does not fully recover. These persistent smell disorders greatly influence daily life. It is thought that COVID-19 causes disorders in smell due to inflammation around the olfactory nerve and in the olfactory pathways. Corticosteroids could reduce this local inflammatory response and improve the sense of smell. The aim of this study is to determine the effectiveness of a short high-dose treatment of oral prednisolone for persistent loss of sense of smell after COVID-19 infection.
Who can participate?
Patients aged 18 years and over with a persistent loss of sense of smell (for over 1 month) within 3 months of a COVID-19 diagnosis
What does the study involve?
Participants are randomly allocated to one of two groups. One group receives prednisolone daily for 10 days. The other group receives matching placebo (dummy drug) treatment. All patients will perform smell training. Participants' sense of smell and taste are assessed and they fill in questionnaires related to their smell and taste ability, quality of life and nasal symptoms.
What are the possible benefits and risks of participating?
The potential benefit is an improvement in smell and a decrease in life-long disability. Treatment with prednisolone can have side effects. There is wide experience with this particular dose, which is generally well tolerated by patients. The main side effects include gastric problems, loss of sleep, mood swings, muscle cramps. Side effects stop after stopping the treatment. The researchers believe that the potential benefits are in proportion with the potential risks.
Where is the study run from?
UMC Utrecht (Netherlands)
When is the study starting and how long is it expected to run for?
February 2021 to March 2024
Who is funding the study?
Netherlands Organisation for Health Research and Development (Netherlands)
Who is the main contact?
Dr Digna Kamalski
d.m.a.kamalski@umcutrecht.nl
Contact information
Public
Heidelberglaan 100- G05.129
Utrecht
3584 CX
Netherlands
| Phone | +31 (0)887556644 |
|---|---|
| d.m.a.kamalski@umcutrecht.nl |
Study information
| Study design | Single-centre double-blind placebo-controlled randomized trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | COrticosteroids for COVID-19 induced loss of Smell (COCOS trial) |
| Study acronym | COCOS |
| Study hypothesis | Loss of smell (anosmia) is common in COVID-19 infections. Most patients regain normal smell within 4 weeks, but in 6-8% the smell does not fully recovery. These persistent smell disorders greatly influence daily life. It is thought that COVID-19 causes disorders in smell due to inflammation around the olfactory nerve and in olfactory pathways. Corticosteroids could reduce this local inflammatory response and improve smell. |
| Ethics approval(s) | Approved 13/10/2021, METC.Utrecht (huispostnummer D01.343, Postbus 85500, 3508 GA Utrecht, The Netherlands; +31 (0)88-7556376; info@metcutrecht.nl), ref: 21-635 |
| Condition | Persistent (>1 month) loss of smell within 3 months of COVID-19 (SARS-CoV-2 infection) diagnosis based on a positive test |
| Intervention | The study will be double-blinded. Participants will be randomly allocated to one of the two groups. Both groups carry the same weight (1:1). Block groups will be 4. Blocks are used to minimise seasonal effects between the groups. The randomisation sequence list on which the patient's number is linked to the study medication is made by the pharmacy. Investigators and patients will be blinded to the randomisation sequence. After finishing all analyses the blinding of researchers and patients to the treatment allocation will be broken. If deblinding is necessary this can be done by the pharmacy at any time One group receives 40 mg of prednisolone daily for the duration of 10 days. The other group receives matching placebo treatment. All patients will perform smell training. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Prednisolone |
| Primary outcome measure | Objective olfactory function measured using Sniffin’ Sticks at baseline, 12 weeks and 12 months |
| Secondary outcome measures | 1. Objective gustatory function measured using Taste Strips at baseline, 12 weeks and 12 months 2. Self-reported smell, taste, parosmia, trigeminal sensations measured using the visual analogue scale (VAS) at baseline, 12 weeks and 12 months 3. Quality of life measured using the questionnaire of olfactory disorders (QoD) at baseline, 12 weeks and 12 months 4. Nasal symptoms measured using Sino-Nasal Outcome Test (SNOT-22) at baseline, 12 weeks and 12 months |
| Overall study start date | 01/02/2021 |
| Overall study end date | 01/03/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 116 |
| Total final enrolment | 115 |
| Participant inclusion criteria | 1. Recent COVID-19 infection (<3 months), confirmed with a positive test 2. Persistent loss of smell after 1 month, objectified by threshold-discrimination-identification (TDI) <30.5 on Sniffin’ Stick test 3. Age 18 years or older, capable of giving informed consent |
| Participant exclusion criteria | 1. Pre-existing olfactory disorders 2. Chronic rhinitis or rhinosinusitis (with or without nasal polyps) 3. Pregnancy 4. Corticosteroids (nasal, oral or intravenously) in last month 5. Contra-indications of steroid use: 5.1. Insulin dependent diabetes mellitus 5.2. Ulcus pepticum |
| Recruitment start date | 15/10/2021 |
| Recruitment end date | 01/03/2022 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Utrecht
3584CX
Netherlands
Sponsor information
Hospital/treatment centre
Heidelberglaan 100
Utrecht
3584CX
Netherlands
| Phone | +31 (0)887555555 |
|---|---|
| info@umcutrecht.nl | |
| Website | http://www.umcutrecht.nl/nl/ |
"ROR" |
https://ror.org/0575yy874 |
Funders
Funder type
Research organisation
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- Netherlands Organisation for Health Research and Development
- Location
- Netherlands
Results and Publications
| Intention to publish date | 01/10/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Planned publication in a high-impact peer-reviewed journal 2. Informing patients through patient association 3. The protocol is under review for publication 4. The data management plan can be accessed at https://dmponline.dcc.ac.uk/plans/83523 5. The first results might be published as early as 01/11/2022 6. The final results might be published by 01/07/2023 |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from DHS-datamanagement@umcutrecht.nl or Dr Digna Kamalski (d.m.a.kamalski@umcutrecht.nl). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 16/11/2022 | 18/11/2022 | Yes | No |
Editorial Notes
18/11/2022: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
22/07/2022: The following changes have been made:
1. The recruitment end date has been changed from 01/04/2023 to 01/03/2022.
2. The intention to publish date has been changed from 01/07/2023 to 01/10/2022.
07/06/2022: Trial's existence confirmed by METC.Utrecht.
