Introduction
You are invited to take part in the CLARITY trial because you have recently been found to have the coronavirus causing COVID-19.
The coronavirus can cause a respiratory infection. Its symptoms include fever, coughing and sore throat. Most people with COVID-19 only have a mild illness, however, in some cases, the illness can be more severe and include symptoms like difficulty breathing. There is no proven treatment for COVID-19 but medical care can manage most of the symptoms while your body fights the infection.
Angiotensin Receptor Blockers (ARBs) are a group of medications that have been widely used for over 20 years in India. They are an existing medication used to treat conditions including high blood pressure, kidney disease and heart disease. ARBs may be able to limit the effect of the coronavirus on the body. This is because the COVID19 virus changes normal body processes to infect lung cells and then promotes inflammation in the lung tissue. Both of these negative effects may be partially blocked by ARBs.
Many people are already taking ARBs for other reasons when they get COVID-19. These people appear to do at least as well as people who are not on ARBs. However, it is not known if the ARB directly improves their recovery from COVID-19. This study aims to assess whether ARBs will reduce the severity of infection in people diagnosed with COVID-19. The trial will continue to recruit participants until there is enough evidence to say whether this is true or not.
Read the information below carefully and ask the study team about anything you do not understand or want to know more about. Before deciding whether or not to take part, you might want to talk about it with a relative or friend.
Medications, drugs and devices have to be approved for use by the Central License Approving Authority, India. The drugs used in this study are an experimental treatment for COVID-19. This means that they are not currently approved for COVID-19 treatment in India but have been used in India for treatment of other conditions such as kidney disease.
Participation in this study is entirely voluntary and there will be no cost to you. If you do take part, you can withdraw at any time without having to give a reason. Whatever your decision, please be assured that it will not affect your current and future medical care in any way. If you do decide to take part in this study, you will need to provide verbal consent which will be audio recorded, where possible. If recording is not possible, a witness who is not a trial staff member will need to listen to the consent process.
By providing verbal consent, you are telling us that you:
- Understand what you have read or have had read to you in the Participant Information Statement
- Consent to take part in the research
- Consent to have the tests and treatments described
- Consent to the use of your personal and health information as described
There are a few reasons why you would not be eligible to participate in this study. These include, but are not limited to, if you have a known intolerance to ARBs, are breastfeeding, have forms of liver disease or regularly experience drops in blood pressure when you go from lying down to sitting up or from sitting to standing. ARBs may affect a developing baby so if you are a woman of child-bearing age (18-51 years), you will need to confirm that you are not pregnant to participate in the study and agree to use an adequate form of contraception for the 28 days of the study. Adequate methods of contraception include hormonal contraception and intrauterine devices. Please discuss contraception options with your treating medical team.
You may participate in the CLARITY trial if you are already participating in other clinical trials, including clinical trials of therapies for COVID-19. The only exception is that you may not participate in CLARITY if the other trial involves ARBs or similar medications. It is possible other trials may not allow you to participate in CLARITY if you are participating in them. Please feel free to discuss this trial and any other trials that you may be eligible for with your treating medical team. You should also inform your treating team and study team if you are currently participating in any other trials at this site or at another hospital.
You will be invited to join the study at participating coronavirus screening clinics and hospitals. A study staff member will discuss the study with you and give you the opportunity to ask questions. You will have 10 days from the date of your coronavirus diagnosis to decide if you wish to participate in this study.
Once enrolled, you will be randomly allocated (like flipping a coin) to start treatment with an ARB, in addition to usual care, or a placebo in addition to usual care. You will have an equal chance of receiving an ARB or placebo. You will continue to receive all standard care for managing your coronavirus infection, which will depend on your specific clinical situation. Both you and your treating doctor will know which treatment you are assigned to.
If you are randomised to receive an ARB, your doctors will prescribe the medication. You will be required to take the medication, which will be a daily tablet taken before you go to bed for a 28-day period, unless your doctor indicates otherwise. Your doctors will decide the starting dose and may adjust the dose, or even withhold it, from time to time. They will make these adjustments in response to your clinical condition, just as they do in usual clinical practice. Same procedures will be applicable in case you are randomised to the placebo group.
It is important to stay hydrated whilst you are unwell, especially if you are experiencing fever. Please ensure that you continue to keep drinking water to stay hydrated. One way of knowing if you are adequately hydrated is by the colour of your urine – if it is too dark, then you need to drink more water. You should also keep an eye out for the amount of urine you are passing, if it seems less than normal, then please mention this to your doctor or nurse.
If you are a woman of child-bearing age (18-51 years), you will need to use an adequate form of contraception during the 28 days of treatment.
The study will collect information on your clinical condition over 90 days. Study staff working within your hospital system will access your medical records to obtain information relevant to the study. This study is being conducted in this way to minimise the intrusion on you and to be efficient for the hospital staff. Study staff working within your hospital system may contact you by phone to collect study information that is not in the medical records, but you are unlikely to be asked to come to hospital for review unless you are unwell.
The information collected from your medical record will include;
Start of Study (Baseline)
- Basic information, including sex, date of birth, and your ethnicity.
- Brief details of your medical history and medication you are taking
- Your smoking history
- Details of your clinical health, including your blood pressure and the state of your breathing and lungs
- A record of your most recent blood test results, either from hospital or from community blood testing.
During the Study (Follow-Up)
- Details recorded about;
- Your medications
- Your clinical health, including your medical observations and test results.
Study staff working within the hospital system will have access to your name and phone number as a means of contacting you. They will only use it for this purpose and are subject to the same privacy regulations that govern routine hospital staff. Your personal identifiers will not leave the hospital system.
All medical treatments involve some risk of harm. The side effects of ARBs in a range of patients are well understood because of the length of time they have been used in routine practice and the number of people that take these medications on a long-term basis. If you notice any side effects and they worry you, tell your doctor. The side effects are usually quite mild with the most common being dizziness or low blood pressure, high potassium, or a headache. These occur in up to 1 in 10 people. Please let your doctor, nurse or study nurse know if you are experiencing these side effects before you take the next tablet.
Serious, but very rare (less than 1 in 1000 people), side effects include allergic reactions, kidney or liver failure, low white blood cells, and swelling of tissues. If you are concerned about serious side effects, please let your treating team know. If you are currently at home, please contact your treating team on [telephone number for site team]. If for some reason, you cannot reach them, please call [Hospital helpline].
If these side effects occur, your doctors may reduce or withhold the ARB treatment. Your doctors are very familiar with the use of these medications. However, the doctors are not familiar with the use of these medications in patients with COVID-19, which is why we are conducting this research study.
Placebo has no side effects. If randomized to placebo, there is a risk that you will not receive the potential benefits of ARBs.
The study medication may or may not be of any benefit to you. We currently do not know whether this treatment will help you, which is why this research is needed. This study aims to improve medical knowledge and may help patients in the future with COVID-19.
New information about the effects of the study medication in COVID-19 may become available during the course of the study. If so, the research team will notify you and your medical team. They may also change or cease the study.
In general, you may receive all routine clinical care. Your treating doctor will discuss your individual treatment with you, including any medications that you can or cannot take during the study.
In routine care you would not receive two different ARBs or an ARB in combination with a similar medication. If you are currently being treated with an ARB, or similar medications like an angiotensin converting enzyme inhibitor (such as Enalapril, Captopril and Perindopril), an aldosterone blocker (such as Eplerenone and Aldactone), angiotensin receptor neprilysin inhibitor (Valsartan/Sacubitril) or aliskiren (Tekturna and Rasilez), you will not be eligible to participate in this study.
While you are participating in this trial please do not take any non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen (e.g. Ibugesic and Intafen), Voveran or Movac. Use of Paracetamol or Aspirin is permitted.
You can choose at any time to withdraw from this study. You do not need to give a reason.
If you wish to discontinue from study medication, you are free to do so without any consequences. It is important to follow everyone’s outcomes to properly understand whether ARBs help treat COVID-19, including the outcomes of people who discontinue the medication. For this reason, we would like to continue to follow your outcomes until 90 days after you enrolled in the study. However, if you do not want us to collect the necessary data to record your outcomes, please tell the study team.
The research team may stop the study or your participation in this study earlier than planned if your treating doctor feels the study is not in your best interests or because the study management or health authorities feel the study needs to be stopped. If this is required it will be discussed with you.
Every reasonable precaution will be taken to ensure your safety during the study. If you suffer any side effects or complications as a result of participating in this research study, please contact your treating doctor as soon as possible and you will continue to receive appropriate medical treatment.
In case of an injury occurring to you during the clinical trial, free medical management shall be given as long as required or until such time it is established that the injury is not related to the clinical trial, whichever is earlier.
In the event of a trial related injury or death, the sponsor or his representative shall provide financial compensation for the injury or death.
A written report of the results will be available to you, by request, at the completion of the study. In addition, the results of the study will be reported in medical and other publications.
All personal information collected for the purposes of this study will be treated confidentially and will be disclosed only with your permission, unless required by law. Your information will only be used for the purpose of this research study. In any study reports or publications your identity will remain confidential.
Any identifiable information obtained in connection with this research will be treated as confidential and securely stored. Only members of the research team or representatives of regulatory authorities may have direct access to it in order to check the accuracy of the information collected and to ensure that the study is being carried out according to local requirements and regulatory guidelines.
Your personal data will not be directly identifiable once it is entered into the study database and transferred to the research team. Any study data shared or published will be coded and not be able to be linked back to you. Any blood samples that we obtain and use will also be used in a coded manner and you will not be directly identified in any of them.
All study data collected will be entered electronically and stored on a REDCap study database. This is a secure, web-based database application, hosted and backed up on the servers at The George Institute for Global Health on a daily basis. No personnel other than the researchers will have access to the research documents. The data will be analysed by the researchers at The George Institute for Global Health. All data for use in journal publications and presentations will be de-identified. The files will be retained for 15 years from the day the study is completed. Once this retention expires, the files will be deleted.
This study is coordinated by The George Institute for Global Health, India and sponsored by George Institute for Global Health, India. Funding for the study will be sought from the Indian Council of Medical Research and other sources
The person you may need to contact will depend on the nature of your query. If you want any further information concerning this study, you can contact the principal Investigator.