Warfarin Anticoagulation in Patients in Sub-Saharan Africa (War-PATH)

July 31, 2023 updated by: Professor Sir Munir Pirmohamed, University of Liverpool

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.

Study Overview

Status

Active, not recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

1500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • South Africa
      • Cape Town, South Africa
        • University of Cape Town
  • Uganda
      • Kampala, Uganda
        • Infectious Diseases Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Self-reported Black African ethnicity from Uganda and South Africa

Description

Inclusion Criteria:

  1. 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).
  2. 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.
  3. Age over 18 years.
  4. Self-reported Black African ethnicity.
  5. Signed or witnessed written (witnessed thumbprint for illiterate participants) informed consent.

Exclusion Criteria:

  1. Patient unwilling to take part.
  2. Patient is, in the opinion of the investigator, not suitable to participate.
  3. Pregnant women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 year
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.
3 years
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.
3+ years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Liverpool

Investigators

  • Principal Investigator: Munir Pirmohamed, University of Liverpool

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 11, 2018

Primary Completion (Estimated)

February 29, 2024

Study Completion (Estimated)

February 29, 2024

Study Registration Dates

First Submitted

February 18, 2018

First Submitted That Met QC Criteria

April 18, 2018

First Posted (Actual)

April 30, 2018

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 31, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UoL001324

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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