Cardiovascular DiseasesWar-PATHNCT03512080
Warfarin Anticoagulation in Patients in Sub-Saharan Africa
An observational study of Cardiovascular Diseases, run by University of Liverpool at 2 sites in 2 countries.
Trial summary
This research programme aims to translate expertise in warfarin anticoagulation from resource-rich to low and middle income countries (LMIC)settings with the goal of improving patient health outcomes. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Cardiovascular Diseases
- How many people
- 681 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 11 Jun 2018to 29 Jul 2024
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Self-reported Black African ethnicity from Uganda and South Africa
Who may be able to join
- Consenting adult patients with either venous thromboembolism (VTE), atrial fibrillation (AF) on warfarin with a target International Normalised Ratio (INR) (INR range 2-3) or valvular heart disease with a target INR (INR range 3-4).
- On a stable maintenance dose for two consecutive clinic visits within the last six months, and the INR was in the therapeutic range at each of those visits.
- Age over 18 years.
- Self-reported Black African ethnicity.
- Signed or witnessed written (witnessed thumbprint for illiterate participants) informed consent.
Who cannot join
- Patient unwilling to take part.
- Patient is, in the opinion of the investigator, not suitable to participate.
- Pregnant women.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: National Institute of Health Research (NIHR) Global Health Research Group on Warfarin Anticoagulation in Patients with Cardiovascular Disease in Sub-Saharan Africa
This research programme aims to translate expertise in warfarin anticoagulation from resource-rich to low and middle income countries (LMIC)settings with the goal of improving patient health outcomes.
An observational study which will be used to develop warfarin dosing algorithms - the ultimate aim will be to ascertain whether these algorithms increase time in the therapeutic range, reduce bleeding and thrombotic risks, and clinic visits for International Normalised ratio (INR) monitoring. Two algorithms will be developed: the first will take into account clinical and geographical factors ("clinical algorithm"), while the second will also incorporate genetic factors in addition to the clinical and geographical factors ("genetic algorithm"). Patients will be recruited from sites in rural and urban Uganda, and in Cape Town, South Africa, to develop a clinical dosing algorithm. It is important to note that there is a wealth of literature data which will be used to define the clinical data that needs to be collected from these patients. To identify genetic factors in African patients, Genome-wide Association Study (GWAS) will be undertaken and any novel factors incorporated into the genetic algorithm - the percentage variation in warfarin dosing explained by the genetic algorithm will be compared with the clinical algorithm.
Read the detailed description
This project focuses on an area unmet clinical need, oral anticoagulation, in patients with a variety of cardiovascular diseases. The investigators' ambition is to translate their internationally renowned expertise in warfarin anticoagulation into low and middle income country (LMIC) settings where it can significantly improve health. By working with policy makers, the investigators will provide the required evidence to allow national roll out of new practices, including the introduction of 1mg warfarin tablets as a quick win to improve dosing accuracy.
This National Institute of Health Research (NIHR) Global Research Group is a collaboration between the University of Liverpool and two low and middle income countries (LMICs), Uganda and 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, valvular heart disease including rheumatic heart disease and prevention of strokes in patients with irregular heart rhythms (atrial fibrillation). Anticoagulation represents an unmet clinical need in Sub-Saharan Africa as patients either do not receive anticoagulation (because of difficulties in monitoring) or are poorly anticoagulated because of poor dosing guidelines. This results in potentially preventable morbidity and mortality which affects the poorer sectors of the population in particular. The investigators have extensive expertise in the United Kingdom and European Union of improving the use of warfarin through the development of novel dosing algorithms, which have now begun incorporating genetic factors.
By contrast, in the investigators' two collaborating partner countries, no locally validated warfarin dosing algorithms exist, even those which only take into account clinical factors. This results in haphazard dosing with the attendant risks of thrombotic or bleeding complications. In both countries, monitoring requires frequent clinic visits, incurring transport costs and missed work days. Patients are often co-infected with human immunodeficiency virus (HIV) and/or Tuberculosis, requiring multiple concomitant medicines which complicate warfarin dosing and dose adjustment.
- Conditions
- Cardiovascular Diseases
- Keywords
- Warfarin, Anticoagulation, Clinical Dosing Algorithm, Genetic Dosing Algorithm, International Normalised Ratio, Uganda, Cape Town, Cardiovascular Disease, Genome-wide Association Study, Stratified Medicine, Pharmacogenetics
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Stable International Normalised Ratio | Consenting adult patients with either venous thromboembolism (VTE), atrial fibrillation (AF) on warfarin with a target International Normalised Ratio (INR) (INR range 2-3) or valvular heart disease with a target INR (INR range 3-4). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of demographic, clinical and genetic factors in an African population that determine daily warfarin dosing requirements
Completion of an audit to evaluate the current quality of anticoagulant services in Cape Town and rural and urban Uganda taking into account the indications, anticoagulant clinic set-up and quality of anticoagulation control.
Measured: 1 year
Development of a clinical algorithm taking into account patient factors, co-medications and underlying disease
Recruitment of patients currently on warfarin will be undertaken to identify clinical and other non-genetic factors associated with poor anticoagulation control to enable development of a warfarin clinical dosing algorithm. Data on patients' age, weight, height, gender, co-morbidities, co-medications, socio-economic factors, warfarin dose history and quality of anticoagulant control (International Normalised ratio (INR) measurement history) will be obtained for the algorithm development.
Measured: 3 years
Development of a validated warfarin dosing algorithm taking into account both clinical and genetic factors
Evaluation of genes specific to the local African populations in Uganda and South Africa that can impact on anticoagulation control will be carried out, resulting in the development of a novel genetic dosing algorithm. In order to identify ethnic specific genetic factors, the investigators will undertake a Genome-wide Association Study (GWAS) on these patients, and any novel genetic factors will be incorporated into an improved dosing algorithm which will be compared with the original algorithm in terms of its ability to predict therapeutic dose.
Measured: 3+ years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2018
- Study start11 Jun 2018
- Primary completion29 Feb 2024
- Study completion29 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 681 participants (actual)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Sir Munir Pirmohamed, University of Liverpool
- Investigators
- Munir Pirmohamed, Principal investigator, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03512080
- Sponsor's protocol ID
- UoL001324
- Acronym
- War-PATH
- Status last verified
- Jul 2024
- First submitted
- 18 Feb 2018
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet. 1996 Sep 7;348(9028):633-8.
PubMed 8782752Avery PJ, Jorgensen A, Hamberg AK, Wadelius M, Pirmohamed M, Kamali F; EU-PACT Study Group. A proposal for an individualized pharmacogenetics-based warfarin initiation dose regimen for patients commencing anticoagulation therapy. Clin Pharmacol Ther. 2011 Nov;90(5):701-6. doi: 10.1038/clpt.2011.186. Epub 2011 Sep 28.
PubMed 22012312Pirmohamed M. Warfarin: almost 60 years old and still causing problems. Br J Clin Pharmacol. 2006 Nov;62(5):509-11. doi: 10.1111/j.1365-2125.2006.02806.x. No abstract available.
PubMed 17061959Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.
PubMed 24251363Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004 Jul 3;329(7456):15-9. doi: 10.1136/bmj.329.7456.15.
PubMed 15231615Sekaggya C, Nalwanga D, Von Braun A, Nakijoba R, Kambugu A, Fehr J, Lamorde M, Castelnuovo B. Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: a case series. BMC Hematol. 2016 Jun 4;16:16. doi: 10.1186/s12878-016-0056-6. eCollection 2016.
PubMed 27274846Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J. 2007 Apr;7(2):99-111. doi: 10.1038/sj.tpj.6500417. Epub 2006 Sep 19.
PubMed 16983400Cavallari LH, Perera MA. The future of warfarin pharmacogenetics in under-represented minority groups. Future Cardiol. 2012 Jul;8(4):563-76. doi: 10.2217/fca.12.31.
PubMed 22871196Mouton JP, Mehta U, Parrish AG, Wilson DP, Stewart A, Njuguna CW, Kramer N, Maartens G, Blockman M, Cohen K. Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey. Br J Clin Pharmacol. 2015 Oct;80(4):818-26. doi: 10.1111/bcp.12567. Epub 2015 Jul 6.
PubMed 25475751
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- National Institute of Health Research (NIHR) Global Health Research Group on Warfarin Anticoagulation in Patients with Cardiovascular Disease in Sub-Saharan Africa
- ClinicalTrials.gov ID
- NCT03512080
- Acronym / sponsor ID
- War-PATH / UoL001324
- Conditions
- Cardiovascular Diseases
- Keywords
- Warfarin, Anticoagulation, Clinical Dosing Algorithm, Genetic Dosing Algorithm, International Normalised Ratio, Uganda, Cape Town, Cardiovascular Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 681 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Study start
- 11 Jun 2018 (actual)
- Primary completion
- 29 Feb 2024 (actual)
- Study completion
- 29 Jul 2024 (actual)
- First posted
- 30 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research programme aims to translate expertise in warfarin anticoagulation from resource-rich to low and middle income countries (LMIC)settings with the goal of improving patient health outcomes.
An observational study which will be used to develop warfarin dosing algorithms - the ultimate aim will be to ascertain whether these algorithms increase time in the therapeutic range, reduce bleeding and thrombotic risks, and clinic visits for International Normalised ratio (INR) monitoring. Two algorithms will be developed: the first will take into account clinical and geographical factors ("clinical algorithm"), while the second will also incorporate genetic factors in addition to the clinical and geographical factors ("genetic algorithm"). Patients will be recruited from sites in rural and urban Uganda, and in Cape Town, South Africa, to develop a clinical dosing algorithm. It is important to note that there is a wealth of literature data which will be used to define the clinical data that needs to be collected from these patients. To identify genetic factors in African patients, Genome-wide Association Study (GWAS) will be undertaken and any novel factors incorporated into the genetic algorithm - the percentage variation in warfarin dosing explained by the genetic algorithm will be compared with the clinical algorithm.
Detailed description
This project focuses on an area unmet clinical need, oral anticoagulation, in patients with a variety of cardiovascular diseases. The investigators' ambition is to translate their internationally renowned expertise in warfarin anticoagulation into low and middle income country (LMIC) settings where it can significantly improve health. By working with policy makers, the investigators will provide the required evidence to allow national roll out of new practices, including the introduction of 1mg warfarin tablets as a quick win to improve dosing accuracy.
This National Institute of Health Research (NIHR) Global Research Group is a collaboration between the University of Liverpool and two low and middle income countries (LMICs), Uganda and 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, valvular heart disease including rheumatic heart disease and prevention of strokes in patients with irregular heart rhythms (atrial fibrillation). Anticoagulation represents an unmet clinical need in Sub-Saharan Africa as patients either do not receive anticoagulation (because of difficulties in monitoring) or are poorly anticoagulated because of poor dosing guidelines. This results in potentially preventable morbidity and mortality which affects the poorer sectors of the population in particular. The investigators have extensive expertise in the United Kingdom and European Union of improving the use of warfarin through the development of novel dosing algorithms, which have now begun incorporating genetic factors.
By contrast, in the investigators' two collaborating partner countries, no locally validated warfarin dosing algorithms exist, even those which only take into account clinical factors. This results in haphazard dosing with the attendant risks of thrombotic or bleeding complications. In both countries, monitoring requires frequent clinic visits, incurring transport costs and missed work days. Patients are often co-infected with human immunodeficiency virus (HIV) and/or Tuberculosis, requiring multiple concomitant medicines which complicate warfarin dosing and dose adjustment.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Target follow-up
- 3 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stable International Normalised Ratio | – | –Consenting adult patients with either venous thromboembolism (VTE), atrial fibrillation (AF) on warfarin with a target International Normalised Ratio (INR) (INR range 2-3) or valvular heart disease with a target INR (INR range 3-4). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Self-reported Black African ethnicity from Uganda and South Africa
Key inclusion criteria (5 listed)
- Consenting adult patients with either venous thromboembolism (VTE), atrial fibrillation (AF) on warfarin with a target International Normalised Ratio (INR) (INR range 2-3) or valvular heart disease with a target INR (INR range 3-4).
- On a stable maintenance dose for two consecutive clinic visits within the last six months, and the INR was in the therapeutic range at each of those visits.
- Age over 18 years.
- Self-reported Black African ethnicity.
- Signed or witnessed written (witnessed thumbprint for illiterate participants) informed consent.
Key exclusion criteria (3 listed)
- Patient unwilling to take part.
- Patient is, in the opinion of the investigator, not suitable to participate.
- Pregnant women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of demographic, clinical and genetic factors in an African population that determine daily warfarin dosing requirements
Time frame: 1 year
Completion of an audit to evaluate the current quality of anticoagulant services in Cape Town and rural and urban Uganda taking into account the indications, anticoagulant clinic set-up and quality of anticoagulation control.
Development of a clinical algorithm taking into account patient factors, co-medications and underlying disease
Time frame: 3 years
Recruitment of patients currently on warfarin will be undertaken to identify clinical and other non-genetic factors associated with poor anticoagulation control to enable development of a warfarin clinical dosing algorithm. Data on patients' age, weight, height, gender, co-morbidities, co-medications, socio-economic factors, warfarin dose history and quality of anticoagulant control (International Normalised ratio (INR) measurement history) will be obtained for the algorithm development.
Development of a validated warfarin dosing algorithm taking into account both clinical and genetic factors
Time frame: 3+ years
Evaluation of genes specific to the local African populations in Uganda and South Africa that can impact on anticoagulation control will be carried out, resulting in the development of a novel genetic dosing algorithm. In order to identify ethnic specific genetic factors, the investigators will undertake a Genome-wide Association Study (GWAS) on these patients, and any novel genetic factors will be incorporated into an improved dosing algorithm which will be compared with the original algorithm in terms of its ability to predict therapeutic dose.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Background: PubMed 8782752Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet. 1996 Sep 7;348(9028):633-8.
- Background: PubMed 22012312Avery PJ, Jorgensen A, Hamberg AK, Wadelius M, Pirmohamed M, Kamali F; EU-PACT Study Group. A proposal for an individualized pharmacogenetics-based warfarin initiation dose regimen for patients commencing anticoagulation therapy. Clin Pharmacol Ther. 2011 Nov;90(5):701-6. doi: 10.1038/clpt.2011.186. Epub 2011 Sep 28.
- Background: PubMed 17061959Pirmohamed M. Warfarin: almost 60 years old and still causing problems. Br J Clin Pharmacol. 2006 Nov;62(5):509-11. doi: 10.1111/j.1365-2125.2006.02806.x. No abstract available.
- Background: PubMed 24251363Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.
- Background: PubMed 15231615Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004 Jul 3;329(7456):15-9. doi: 10.1136/bmj.329.7456.15.
- Background: PubMed 27274846Sekaggya C, Nalwanga D, Von Braun A, Nakijoba R, Kambugu A, Fehr J, Lamorde M, Castelnuovo B. Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: a case series. BMC Hematol. 2016 Jun 4;16:16. doi: 10.1186/s12878-016-0056-6. eCollection 2016.
- Background: PubMed 16983400Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J. 2007 Apr;7(2):99-111. doi: 10.1038/sj.tpj.6500417. Epub 2006 Sep 19.
- Background: PubMed 22871196Cavallari LH, Perera MA. The future of warfarin pharmacogenetics in under-represented minority groups. Future Cardiol. 2012 Jul;8(4):563-76. doi: 10.2217/fca.12.31.
- Background: PubMed 25475751Mouton JP, Mehta U, Parrish AG, Wilson DP, Stewart A, Njuguna CW, Kramer N, Maartens G, Blockman M, Cohen K. Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey. Br J Clin Pharmacol. 2015 Oct;80(4):818-26. doi: 10.1111/bcp.12567. Epub 2015 Jul 6.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Munir Pirmohamed principal investigator
University of Liverpool
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases, run by University of Liverpool at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of demographic, clinical and genetic factors in an African population that determine daily warfarin dosing requirements (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03512080, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.