PRE-EMPTIVE PHARMACOGENOMICS IN ACUTE CARE SETTINGS WITH HEALTH ECONOMIC EVALUATIONS (PHOENIX TRIAL)

Not Applicable

Recruiting

• Conditions: Pharmacogenomic Drug Interaction

• Registration Number: NCT06907784
• Lead Sponsor: NHS Greater Glasgow and Clyde

Brief Summary

It is known that individuals respond differently to the same medicine with some people benefitting, some experiencing no effect and others suffering side-effects or even coming to harm. Some of the differences in response to medications can be explained by our genes. Genes are short sections of DNA. Each individual has over 20,000 different genes. Genes carry instructions for making the proteins needed to build things within the body including the sites where medicines act. Pharmacogenomics is the study of how our genes affect the way our body responds to medications.

Doctors can test for gene variations that might put an individual at risk of severe side-effects or mean that they are likely to receive no benefit from a specific medicine. Though not widely available in the NHS, testing allows doctors and patients to chose a different dose or avoid the medicine completely. It is estimated that almost everyone in the population (\>95%) carries at least one gene variation that affects our response to medicines.

The PHOENIX study will recruit 4,000 participants who are admitted to hospital or attend an outpatient clinic who require a new drug prescription. The new drug prescription will be one who known pharmacogenomic implications. A cheek (buccal) swab will be taken which can be used to test a large number of genes known to alter the response to medicines. Around half of the participants will be tested immediately whilst the other half will have the test after three months. The results of the test relevant to each patients new prescription will enable the doctor prescribing to determine if any changes to that medicine would be beneficial. Information will be collected about participants quality of life, subsequent admissions to hospital, medication changes and side-effects. An assessment of cost saving to the NHS will also be made.

Detailed Description

PHOENIX is a pilot two-group parallel randomised trial aimed at generating preliminary evidence on the effectiveness of a pharmacogenomics (PGx) intervention in reducing adverse drug reactions (ADR) and treatment failures in patients (hospitalised or attending secondary care specialist clinics). Additionally, it will provide early insights into health-economic impact of such PGx-guided care. Pharmacogenomic analysis will be conducted on DNA extracted from buccal swab samples taken at consent. This Trial will be performed according to the UK Policy Framework for Health and Social Care Research (2023).

The trial will recruit adult participants, admitted to wards or attending specialist outpatient clinics in Queen Elizabeth University Hospital (QEUH), Glasgow, where the selected PGx drugs are frequently prescribed: General Medicine (all specialities and receiving areas), Medicine for the Elderly, Cardiology, Stroke, Diabetes and Endocrinology, Infectious Diseases, Rheumatology, Neurology, General Surgery, Vascular Surgery, Urology, ENT and Orthopaedics.

Potential participants will be identified by the prescription of a new medicine with pharmacogenomic implications on the HEPMA electronic prescribing system, trial team visit to ward areas, treating clinician or patients self identifying on inpatient ward areas. Drug caps will be in place throughout the trial to prevent over-recruitment of one or more commonly prescribed medications. Potential participants approached by study team and offered PIS/invite. Potential participants contact study team to opt-in or study team return to ask if interested in study +/- further discussion. Written informed consent will be given by each participant or their legal representative is they are deemed to be lacking capacity.

Maximum Total 4000 Intervention arm: 1000 to 2000 Standard of care arm: 1000 to 2000

All participants will provide a buccal swab (mouth swab) for genetic testing. All samples will have DNA extracted on receipt of the sample. Pharmacogenomic testing will be performed immediately for those in the intervention arm or stored and tested at six month in the standard of care arm.

The pharmacogenomic report will be returned to the clinician with responsibility for the patients care (at baseline for intervention or three months for standard of care) with a recommendation regarding the medicine if changes are suggested. This will unblind the treating clinician and potentially the patient if medication changes are made for the intervention group.

All participants will be asked to complete questionnaires on quality of life (monthly for three months), medication adherence and adverse drug reactions (monthly for three months).

Blood testing will be carried out for safety (usual clinical care) at approximately four weeks, dependent on the index drug.

Further information will be collected through West of Scotland Safe Haven on new medication prescriptions, hospital admissions and deaths. This will require the participants CHI (community health index) number to be linked to their Safe Haven data but data will be returned to the researchers in anonymised form.

Study Timeline

• Study First Submitted: 2025-03-14
• Study First Submitted QC: 2025-03-31
• Study First Posted: 2025-04-02
• Study Start: 2025-04-09
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-14
• Primary Completion: 2026-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Composite of ADRs and/or treatment failures	3 months	Composite of ADRS (CTCAE ≥2) and/or treatment failures (applies to specific drugs where treatment failure is captured by hospital admissions with the condition for which the index drug was commenced).

Secondary Outcome Measures

Name	Time	Method
5-level EQ-5D version (EQ-5D-5L) EuroQol	3 months	Assess changes in quality of life using the EQ-5D-5L questionnaire administered monthly over three months to explore the impact of PGx-guided care on participants' overall well-being.; The EQ-5D-5L questionnaire will comprise of ive dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.; The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS
Frequency of Actionable Genotypes at Baseline	7 days	Report the frequency of actionable genotypes that lead to drug/dose selection or modification of all drugs, including the index drug, at baseline.
Self-Reported Adverse Drug Events (ADEs):	3 months	Collect data on all frequencies of self-reported ADEs, regardless of severity or drug-gene association, monthly over three months, providing a participant-centered view of drug tolerability.
PGx Result Utilisation in Intervention Arm	3 months	Measure the proportion of participants in the intervention arm who receive at least one drug/dose selection or modification based on PGx test results, offering insight into clinical application.
PGx Result Utilisation in Standard Care Arm (Post-Delayed Genotyping)	3 months	For participants in the standard care arm, determine the proportion who receive at least one drug/dose modification after delayed genotyping, highlighting the potential impact if PGx results were available at baseline.
Ordinal analysis of adverse drug reaction (ADR) severity	3 months	Evaluate ADR severity across different grades using NCI-CTCAE criteria and logistic ordinal regression to understand the impact of PGx-guided prescribing on ADR intensity.
Incidence of clinically relevant adverse drug reactions (ADR)	3 months	Track the occurrence (incidence) of clinically relevant ADRs caused by the index or subsequent drugs as a binary outcome to preliminarily assess the safety of PGx-guided medication selection.
Dose Adjustments for Index Drug	3 months	Record the frequency of dose adjustments made for the index drug, capturing how PGx information influences pharmacotherapy adjustments.
Drug cessation due to lack of efficacy	3 months	Track discontinuations (frequency) of drugs due to lack of efficacy, providing a preliminary measure of the therapeutic effectiveness of PGx-guided prescribing.
14. Additional Prescribed Drugs During Follow-Up	3 months	Count additional drugs prescribed (frequency of additional drugs prescribed) during the follow-up period to gauge the potential broader impact of PGx testing on medication management complexity.
Frequency of Actionable Genotypes for New Prescriptions During Follow-Up	7 days - 3 months	Report frequencies of actionable genotypes that indicate drug/dose selection or modification for any new prescriptions issued between 7 and 90 days post-randomisation.
Serious adverse drug reactions	3 months	Focus on serious ADRs (frequency of ADRs) occurring within three months post-index drug administration to gain insights into the immediate safety impacts of PGx-guided versus standard care.
Serious self reported adverse drug events (ADEs)	3 months	Track serious ADEs (frequency of ADEs) reported by participants, adding depth to the safety evaluation and focusing on participant-experienced impact
Drug cessation due to adverse drug reactions (ADRs)	3 months	Monitor instances (frequency) of where the index drug is discontinued because of ADRs, offering a direct measure of drug tolerability under PGx-guided care.
Changes in Drug Adherence	3 months	Evaluate changes in adherence scores from baseline to three months, exploring the influence of PGx testing on participant engagement and compliance. This will be assessed using the Medication Adherence Report Scale (MARS-5 questionnaire). Individual items will be scored 5 = never to 1 = always) i.e. high scores = high adherence. The total individual scores together to form a scale score (range = 5 to 25). Then an adjusted mean score is calculated by dividing the scale mean by the number of items in the scale (range 1-5).\* The distribution of scores to see whether the scale should be dichotomised or left as a continuous scale. (In some data sets reported adherence is heavily positively skewed and in this case it might be advisable to dichotomise on the basis of the frequency distribution).; \*Point 3 is included to facilitate comparison across data sets where different versions of the MARS have been used (e.g. MARS-5: MARS-10 etc).
Participant Perspectives	3 months	Gather participants' perspectives on PGx testing through a survey administered at three months post-randomization, providing insights into participant experience and perceived value of PGx-guided care.

Trial Locations

Locations (1)

Queen Elizabeth University Hospital; 🇬🇧 Glasgow, United Kingdom