NIHR Global Health Research Group on warfarin anticoagulation in patients with cardiovascular disease in Sub-Saharan Africa (War-PATH)
The WarPATH NIHR Global Research Group is a study between the University of Liverpool, Infectious Diseases Institute, Uganda and University of Cape Town, South Africa. It will focus on a clinically important non-communicable disease area which requires the use of anticoagulation. Anticoagulants, in particular warfarin, are used in these countries for the treatment of venous thromboembolism, rheumatic heart disease and prevention of strokes in patients with irregular heart rhythms (atrial fibrillation).Doses have to be constantly monitored, however, since variations in genetic makeup, age and size can cause either too small an effect from the medicine or even too much – the latter can cause bleeding in patients.
Anticoagulation with warfarin is an important area of unmet medical need in African countries because of the lack of validated dosing algorithms and/or monitoring facilities. We have extensive expertise in the UK and EU of improving the use of warfarin through the development of novel dosing algorithms, which have now began incorporating genetic factors. This group aims to improve anticoagulation by developing clinical dosing algorithms, and further improve anticoagulation quality by using novel technological advances.
The study will take part in Haematology Clinics and Departments in Uganda and Cape Town, South Africa. To see if your hospital is taking part in this study please go to recruiting centres.
This study has been funded by the National Institute for Health Research's (NIHR) Global Health Research (GHR) Programme (ref: 16/137/101).
University of Liverpool, Liverpool, United Kingdom; Infectious Diseases Institute, Kampala, Uganda; University of Cape Town, Cape Town, South Africa.
The study has been reviewed by research ethics committees in Uganda, South Africa and United Kingdom, who have agreed the study is being conducted in a correct and appropriate manner.
Why are we doing this research study?
Warfarin is a medicine that stops the blood from forming clots. Warfarin is used to treat patients who already have blood clot disorders. These disorders include blood clots in the veins of the legs (deep vein thrombosis) and clots that form in the lung (pulmonary Embolism or “PE”). In some patients, warfarin can also be used to prevent blood clots forming in the heart or brain, in patients with some heart diseases and in patients that have had surgery on their hearts.
Doctors usually use a standard dose when starting patients on warfarin. However, not everyone responds to treatment with warfarin in the same way. Some patients respond poorly to warfarin treatment and may continue to form clots. Other patients respond to warfarin too strongly and their blood thins too much. They may have bleeding as a result, which can be serious. We want to know the reasons one patient may require a different dose of warfarin from another patient.
Warfarin dosing has not been well studied in sub-Saharan Africa. The purpose of this study is to collect information about warfarin dosing in black African patients. We are also collecting samples for genetic testing. You can participate in the study even if you choose not to give a sample for genetic testing. Age, weight, diet, male or female sex and other medication have been shown to be important for correct warfarin dosing in other parts of the world, but this has not been well studied in black South African or Ugandan patients.
When a person is taking warfarin, their nurse or doctor will request regular International Normalised Ratio (INR) tests to see if the warfarin has thinned the blood enough. This test is performed regularly as part of the person’s usual care. The results of the INR tests help your doctor to decide what dose of warfarin you need to take.
What is being tested?
In this study we will collect clinical information about patients treated with warfarin in Cape Town who have an INR that is in the target range. The information that we will collect will include age, weight, other illnesses that patients have and other medications that they are taking, as well as results of laboratory tests.
We will use information collected in this study, including the results of genetic testing, to identify the important factors doctors should consider when they choose warfarin doses for black African patients. We plan improve dosing guidelines. We will use the information we collect to develop an algorithm (a set of rules to follow) that will help doctors and nurses to pick the correct warfarin dose for their black patients.
We have approached you because you are taking the medicine warfarin as an anticoagulant (blood thinner).
Do I have to say yes?
It is up to you to decide whether or not to take part. If you do decide to take part you will be given an information sheet to keep and be asked to sign a consent form. You will still be free to withdraw at any time and without giving a reason. This will not affect the standard of care you receive. If you do decide to withdraw at a later stage, any blood samples you have provided will be removed and destroyed. Any research results obtained prior to your withdrawal of consent will however be used. To withdraw your consent, you must contact your study doctor, because only he/she has access to all of your identifying information.
What will happen if I take part?
Taking part in this study will not affect your usual clinical care in any way. You will continue to take all current medications and continue with any planned treatments, as prescribed by your clinician.
If you decide to take part, you will be seen by a research clinician when attending your clinic. The research clinician will: Take some details including your age, height, weight, ethnic origin, past medical history, current medications, alcohol and smoking history. Further details will be obtained from your case notes and hospital, pharmacy and laboratory records including information regarding your warfarin treatment (reason for treatment, current and previous dose, duration of treatment, target and test results of your INRs).
Are there any risks to taking part?
There will be some minor but short-lasting discomfort from having a blood test e.g. bruising and some pain at the site where the blood is taken. Taking part in the study will not affect your current treatment, nor will it affect your ability to obtain insurance for health purposes.
Are there any benefits of taking part?
It is unlikely that the study will be of direct benefit to you, however, it may benefit you and other patients who are prescribed warfarin in the future.
Who is doing this research?
This study is funded by the National Institute for Health Research, UK and is shared work between the University of Liverpool, United Kingdom, the University of Cape Town, South Africa and the Infectious Disease Institute, Kampala, Uganda.
Why are you taking blood for genetic testing?
The code in the cells of the human body is called DNA (deoxyribonucleic acid). Some parts of the DNA are code for “genes”. Each of these genes is a set of instructions. These instructions determine what we look like, and control the functioning of our bodies. Our genes control how we break down substances in our bodies, including drugs. The “genome” is all of a person’s DNA.
Recent research studies in the US and in Europe have shown that there are specific genes that are important for warfarin dosing in patients with European ancestry. We do not know how important these genes are for warfarin dosing in patients of African ancestry. We will use your genetic specimen, together with information we collect about you and your warfarin dosing, to find out what genetic factors are important for warfarin dosing in African patients.
We will do a genome wide association study (GWAS) where we look across the whole genome (all of the DNA in your cells) for genetic factors that are important for warfarin dosing in black African patients.
We will also test genes that have been shown to be important in patients of European ancestry, to see if there are changes in these genes that are also important in black African patients in South Africa and Uganda.
We will use the results of the GWAS and targeted genetic testing to work out if adding genetic testing into dosing algorithms for black patients makes it easier to decide what dose of warfarin will get a patient’s INR into the target range.
The following 11 sites will be participating1 Groote Schuur Hospital, Cape Town, South Africa
The Chief Investigator
Lead Investigator – Uganda
Lead Investigator – South Africa