Information for staff participants (Patient Information Sheet)
You can read the Patient Information Sheet in the expandable sections below; it is also available as a pdf and consent form to download and print.
Currently, there are no specific licensed or approved drugs for the disease; and with the number of confirmed cases of COVID-19 infection arising from the SARS-CoV-2 coronavirus expected to rise substantially and rapidly, this has the potential to overwhelm the ability of the National Health Service (NHS) to cope with the increased demand.
Hydroxychloroquine is commonly used to treat malaria and rheumatological conditions and its side effects are well-known. The doses used in this trial are at the lower end of the range of normal treatment doses prescribed for the conditions they are licensed for, so side effects may be less likely to occur.
This is a double-blind trial meaning neither you nor the trial doctor will know which treatment you have been assigned to.
We believe Hydroxychloroquine may offer protection against developing symptoms/contracting the virus. We plan to include 1,200 participants who are NHS frontline healthcare workers from at least 3 hospitals across the UK.
If you decide to participate you will be asked to sign an Informed Consent Form, however you are still free to change your mind and leave the trial at any time without giving a reason. If you choose not to participate or to leave the trial, your future medical treatment will not be affected in any way.
As we don’t know whether Hydroxychloroquine can reduce the risk of healthcare workers contracting the coronavirus, or whether the dose of Hydroxychloroquine as a prevention treatment is important, we need to compare the treatment (Hydroxychloroquine) with Placebo in different dosing regimens.
There are 3 groups in this study and each group will receive a different treatment. You will be allocated one of the groups for this trial in a random way (by chance) using a computer algorithm. You will have a 3:3:2 chance of receiving either:
- Hydroxychloroquine daily (loading dose of 2 x 200mg twice daily for first two days (800mg/day), then dosed daily; 200mg/day) plus weekly placeboli;
- Hydroxychloroquine weekly (loading dose of 2 x 200mg twice daily for first two days (800mg/day), then dosed weekly; 400mg/week) plus daily placebo; or
- Placebo (loading dose of 2 tablets twice daily for first 2 days, then dosed daily with an additional 2 tablets weekly).
Below is a list of the assessments and procedures that we will carry out in the trial. Some assessments rely on local logistics and/or NHS resources and if not undertaken will not affect your participation in the trial. These include COVID-19 tests, respiratory screens and blood samples across visits 1-3, as outlined below:
- Visit 1: Baseline (duration, approximately 45 minutes at hospital): Where possible, we will perform a standard COVID-19 test/s (this may not be analysed until a later date due to current limitations in obtaining results) and respiratory screen for common respiratory viruses. These will be taken by nasal and throat swab, or blood, as per current clinical practice guidelines at each visit. We will ask you about your medical history, concomitant medications, and current work setting.
You will also be invited to give a blood sample (blood group, serum and genetic store; the maximum amount of blood taken will be approximately 30ml [2 tablespoons] at each visit).
We shall then explain how to complete some simple / brief questions to monitor your health weekly. These can be completed over web/app-based interfaces or telephone.
Following this, you will be randomised to a treatment group and given your treatment pack containing your trial medication for the first 7 weeks.
- Visit 2: Interim> (duration, approximately 45 minutes at hospital): This will take place approximately 6 weeks after baseline Visit 1. You should not take your trial medication on the morning of this visit. Where possible, we will perform a second COVID-19 test/s and respiratory screen as before.
We will review your current work setting, concomitant medications, and ask about any adverse events you may have experienced. You will also be invited to give another blood sample (drug levels and serum store).
- Visit 3: End of study (duration, approximately 45 minutes at hospital): This will take place once you have completed your trial medication, approximately 13 weeks after baseline visit 1.
Where possible, we will perform a final COVID-19 test/s and respiratory screen. We will review your current work setting, concomitant medications and ask about any adverse events. You will be invited to give a final blood sample (serum store).
- Weekly assessments (duration, approximately 5-10 minutes performed remotely via telephone or web/app interface): These will be undertaken weekly for 13 weeks, 2 of which will be conducted during hospital visits 2 and 3.
We shall ask you to confirm you have taken your medication over the preceding week, and report any new or review any ongoing adverse events. We will also ask you to complete brief questions to assess your symptoms, self-reported recovery and incidence of health care usage.
Between hospital visits you will need to complete some brief questions remotely via telephone/online/web-based interface on a weekly basis. You should continue to use PPE as recommended by PHE and your hospital guidelines at all times during this study.
It is important that you take any trial medication regularly as directed by your trial doctor. You will be given 3 bottles of identical medication with instructions on when to take doses from each bottle.
It is important that you follow these instructions carefully to ensure that you are taking the correct medication at the correct interval. This will occur for the loading and maintenance phases.
On visit 2 you will receive the remainder of the trial medication with instructions to complete the maintenance phase. Trial medication should be taken at roughly the same time each day. The table below shows dosing regimes for both the loading phase and maintenance phase of the trial. (Click on the image to enlarge.)
Administration of medication:
Each dose should be taken with a meal or glass of milk and tablets swallowed whole.
Missed or replacement doses:
Do not replace vomited doses. Do not make up for missed doses by taking extra tablets if more than 12hrs has elapsed after the time it/they would usually be taken. In the event of missed doses, do not double the number of tablets to make up the missed dose.
Any unused study treatment must be returned to the study site.
Permitted and prohibited medications:
Over-the-counter medications such as paracetamol (doses <2.0g/day) are permitted. Grapefruit and/or grapefruit juice should be avoided. Antacids should be avoided within ~4 hours of dosing. You should tell the trial team if you feel unwell or different in any way. If you have any major concerns or are feeling very unwell please contact your trial doctor immediately using the contact numbers below. If you experience potential COVID-19 symptoms or become NHS COVID test positive/COVID positive during the trial you should contact the trial doctor immediately and stop taking your trial medication. You should discuss your participation in this trial with any insurance provider you have (e.g. protection insurance, life insurance, income protection, critical illness cover and private medical insurance) and seek advice if necessary, as failure to notify them may affect or invalidate your cover.
As such, side effects may be less likely to occur and are unlikely to result in significant adverse events. These risks will be assessed in every participant.
Common (less than 10% of patients):
- abdominal pain
- decreased appetite
- feeling sick
- mood changes
- skin rash
Uncommon (less than 1% of patients):
- hypoglycaemia (low blood sugar)
- loss of hair (alopecia)
- worsening of eyesight
- blurred vision
- double vision anxiety
- leg or arm weakness
- tingling or numbness
- ringing in the ear (tinnitus)
- feeling dizzy
- sensation of unsteadiness or spinning (vertigo)
- low blood or platelet count
Hydroxychloroquine is also associated with other potential ophthalmic side effects including reduced visual acuity, reduced peripheral vision and nocturnal visual impairment.
However, these side effects are associated with prolonged use of hydroxychloroquine (>5 years) and the Royal College of Ophthalmologists advise annual screening for retinal disease for treatment durations of 5 years or longer.
There is also a risk of QT prolongation associated with hydroxychloroquine use, but this risk is extremely low when the duration of hydroxychloroquine treatment is short-term (as in the current trial) and at the doses used in this trial.
However, individual patients can react differently to the same drug which means that there is a possibility of experiencing side effects.
In addition, if you are diabetic and taking medication for your diabetes, there is a small risk of hypoglycaemia during the 2-day loading phase of the trial.
You will be encouraged to monitor your blood glucose levels carefully during this period, and to consume a bed-time snack if possible. The trial doctor will monitor any side effects regularly and take appropriate actions where necessary.
However, information collected as part of your participation in this trial may benefit patients with COVID-19 or healthcare workers or other individuals who come in contact with COVID-19 patients in the future.
Once the trial has ended the study drugs may not be available to healthcare workers. However, pending the results of the trial, treatment guidelines may change.