efficacy of LOw dose antihypertensive and lipid lowering pill combinations To improve stroke oUtcomeS (LOTUS)
A randomised trial to compare outcomes on hypertension and hypercholesterolaemia with single pill combination based therapy and telehealth intervention vs standard care in survivors of ischaemic stroke/transient ischaemic attack.
The George Institute for Global Health Australia
400 participants
Oct 23, 2025
Interventional
Conditions
Summary
LOTUS is an investigator-initiated and nurse-led trial with a two-arm, open-label, randomised, multicentre design. Low dose combination therapies for treatment of hypertension and (optional factorial arm) hypercholesterolaemia will be compared to usual care in stroke survivors over 26 weeks. The primary aim of LOTUS is to assess whether an innovative model of care involving low dose antihypertensive (and optionally) lipid lowering treatment underpinned by team-based, telehealth-supported care will reduce BP over 26 weeks when compared to usual care in survivors of ischaemic stroke/transient ischaemic attack (TIA). Secondary aims include if this new model (when compared to usual care): reduces cholesterol, is acceptable to patients and clinicians, is cost-effective, improves medication adherence and patient acceptability, and is safe.
Eligibility
Inclusion Criteria6
- Free & informed consent (paper or electronic)
- Adult aged 18 years or over,
- Recent ischaemic stroke/Transient ischaemic attack in the past 12 weeks, as diagnosed by a neurologist.
- Indicated for pharmacological treatment of high blood pressure.
- Optional factorial arm:
- Indicated for pharmacological treatment of high cholesterol
Exclusion Criteria13
- Intracerebral or subarachnoid haemorrhage.
- Contraindication to any of the individual components of the intervention.
- Unable to complete trial procedures.
- Planned overseas travel in the first 30 days of joining the trial and if planning to travel for longer than 1 months during the trial period.
- Pregnant or had a positive pregnancy test or unwilling to undertake a pregnancy test during the screening, or breastfeeding.
- Of childbearing age and not using an acceptable method of contraception.
- Documented evidence of secondary cause of hypertension e.g. renal artery stenosis
- History of significant renal impairment (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73m2) in last 12 weeks.
- Treatment resistant hypertension i.e. not controlled despite taking 3 or more BP-lowering drugs, including maximum dose of medications.
- Concomitant illness, physical impairment or mental condition which in the opinion of the investigator/treating doctor could interfere with the conduct of the trial including outcome assessments.
- Concomitant medications that cannot be stopped, switched or adjusted, which in the opinion of the investigator/treating doctor could interfere with the conduct of the trial: e.g. cautious use with other drugs such as non-steroidal anti-inflammatory drugs.
- Optional factorial arm:
- Unsuitable for randomisation as they are already prescribed combination LDL lowering therapy (i.e., statin with ezetimibe or PCSK9 inhibitor).
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Interventions
Acronyms: GMRx2 - A single pill combination of Telmisartan/Amlodipine/Indapamide, available in Quarter (1/4) strength (10/1.25/0.625), Half (1/2) strength (20/2.5/1.25), and Standard strengths (40/5/2.5). SPC – Single Pill Combination BP - Blood Pressure CT - Combination Therapy Study Interventions – SPC based care: At randomisation, if the participant is randomised to SPC based care, they will initially be prescribed GMRx2 ¼ if not on any pre-existing BP therapy. If already on pre-existing BP therapy, they will be prescribed an appropriate dose of GMRx2 by the investigator. During follow-up visits, if the average of two home BP measurements is above 130 mmHg SBP and/or above 80 mmHg DBP, BP-lowering therapy will be up titrated by the nurse with support from the investigator in the following order: GMRx2 – triple 1/4 (telmisartan 10 mg, amlodipine 1.25 mg, indapamide 0.625 mg) Then GMRx2 – triple 1/2 (telmisartan 20mg, amlodipine 2.5mg, indapamide 1.25mg) Then GMRx2 – standard dose (telmisartan 40mg/amlodipine 5mg/indapamide 2.5mg) Then GMRx2 – standard + telmisartan 40 mg/amlodipine 5mg CT Then GMRx2 – standard + telmisartan 40 mg/amlodipine 5mg CT + spironolactone 25mg. It is preferred that the above sequence for up-titration is adhered to. However, clinicians may choose to vary the above recommended regimen at their own discretion. Participants will take their prescribed dose once daily for 26 weeks. Participants will be instructed to return all remaining medication at each clinic visit to be counted by the research nurse or pharmacist. The Medication Accountability ARMS-7 questionnaire will be completed at 12 and 26 weeks post randomisation. Optional Cholesterol Lowering Factorial Arm: Combination Therapy of rosuvastatin/ezetimibe 10mg/10mg for patients indicated for pharmacological treatment of high LDL. The low-dose combination LDL lowering strategy to be tested here will not have up titration steps. Participants will take their prescribed dose once daily for 26 weeks. Participants will be instructed to return all remaining medication at each clinic visit to be counted by the research nurse or pharmacist. The Medication Accountability ARMS-7 questionnaire will be completed at 12 and 26-weeks post randomisation. Treatment Arms/groups: Arm 1: BP Lowering Strategy (SPC of Telmisartan/amlodipine/indapamide) Arm 2: BP Lowering Strategy (SPC of Telmisartan/amlodipine/indapamide) + Cholesterol Lowering Optional Factorial Arm (Rosuvastatin 10mg/Ezetimibe 10mg CT) Arm 3: Cholesterol Lowering Optional Factorial Arm (Rosuvastatin 10mg/Ezetimibe 10mg CT) Arm 4: Usual Care
Locations(19)
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ACTRN12624001279516