Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension
NCT ID: NCT04518293
Last Updated: 2025-06-03
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
1385 participants
INTERVENTIONAL
2021-07-09
2023-09-01
Brief Summary
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Detailed Description
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GMRx2: Single pill combinations of telmisartan/amlodipine/indapamide Dose version 2: telmisartan 20mg/amlodipine 2.5mg/indapamide 1.25mg Dose version 3: telmisartan 40mg/amlodipine 5 mg/indapamide 2.5mg INDICATION: Hypertension TRIAL DESIGN: International, multicenter, randomized, double-blind, active controlled, parallel-group.
OBJECTIVES: To investigate the efficacy and safety of GMRx2 compared to dual combinations
INTERVENTION:
Single-Blind Active Run-In Period. Enrolled participants will be asked to discontinue their current BP-lowering drug(s) and undergo a single-blind active run-in period for 4 weeks with GMRx2 dose version 2. Participants will be advised to take the capsule once daily in the morning at approximately the same time each day. For days on which BP is being measured, the capsule should be taken directly after the morning home BP measurement.
Double-Blind Treatment Period. Participants still eligible after the run-in period will be allocated in a double-blind fashion to one of the following 4 randomized groups: GMRx2 dose version 2, or telmisartan 20mg+amlodipine2.5mg, or telmisartan 20mg+indapamide 1.25mg, or amlodipine 2.5mg+indapamide 1.25mg. At week 6 all doses will be doubled.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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GMRx2
Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Single pill
telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
Single pill
Dual - TA
Telmisartan 20 mg/amlodipine 2.5 mg . At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg
Telmisartan 20 mg/amlodipine 2.5 mg
oral tablet
telmisartan 40 mg/amlodipine 5 mg
oral tablet
Dual - TI
Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg
Telmisartan 20 mg/indapamide 1.25 mg
oral tablet
telmisartan 40 mg/indapamide 2.5 mg
oral tablet
Dual - AI
Amlodipine 2.5 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to amlodipine 5 mg/indapamide 2.5 mg
Amlodipine 2.5 mg/indapamide 1.25 mg
oral tablet
amlodipine 5 mg/indapamide 2.5 mg
oral tablet
Interventions
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Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Single pill
telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
Single pill
Telmisartan 20 mg/amlodipine 2.5 mg
oral tablet
telmisartan 40 mg/amlodipine 5 mg
oral tablet
Telmisartan 20 mg/indapamide 1.25 mg
oral tablet
telmisartan 40 mg/indapamide 2.5 mg
oral tablet
Amlodipine 2.5 mg/indapamide 1.25 mg
oral tablet
amlodipine 5 mg/indapamide 2.5 mg
oral tablet
Eligibility Criteria
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Inclusion Criteria
1. Provided signed consent to participate in the trial.
2. Adult of age ≥18 years.
3. Attended automated clinic seated mean systolic blood pressure (SBP) (average of last 2 measurements calculated by the device):
140-179 mmHg on 0 BP-lowering drugs, or 130-170 mmHg on 1 BP-lowering drug, or 120-160 mmHg on 2 BP-lowering drugs, or 110-150 mmHg on 3 BP-lowering drugs.
At randomization visit
1. Home seated mean SBP 110-154 mmHg in the week prior to the randomization visit.
2. Adherence of 80-120% to run-in medication.
3. Tolerated run-in medication.
4. Adherence to home BP monitoring schedule: in the week before randomization, at least 6 measures (e.g. ≥2 sets of triplicate measures, ≥3 sets of duplicate measures) including at least 1 morning and 1 evening each with ≥2 measures. Morning is defined as any measure in the am and evening as any measure in the pm. Morning and evening do not have to be same day.
Exclusion Criteria
1. Receiving 4 or more BP-lowering drugs.
2. Receiving any BP lowering drugs for indications other than hypertension e.g. heart failure
3. Pregnant or had a positive pregnancy test or unwilling to undertake a pregnancy test during the trial and up to 30 days after the discontinuation of the trial medication or breastfeeding or of childbearing age and not using an acceptable method of contraception. Acceptable methods of birth control include hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (e.g. condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization. Contraception should be used for at least 1 month before the screening visit and until the end of trial participation.
4. Not suitable for participation in a clinical trial according to local ethical or regulatory requirements related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
5. Contraindication, including hypersensitivity (e.g. anaphylaxis or angioedema), to the active run-in treatment or to any of the trial medication options in the four randomized groups.
6. Current/history of transient ischemic attack, stroke, or hypertensive encephalopathy.
7. Current/history of acute coronary syndrome, unstable angina, myocardial infarction, percutaneous transluminal coronary revascularization, or coronary artery bypass graft.
8. Current atrial fibrillation. Patients with a history of paroxysmal atrial fibrillation are potentially eligible as long as there has been no episode in the last 3 months, while patient with a history of persistent or permanent atrial fibrillation are not eligible.
9. Current/history of New York Heart Association class III and IV congestive heart failure.
10. Current/history of a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.
11. Current/history of substantially uncontrolled diabetes (HbA1c \> 11.0%) within last three months.
12. Current/history of end-stage renal disease or anuria or estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73m2.
13. Electrolyte levels that would be regarded as contraindications for any of the potential treatment arms e.g. serum sodium \<132mmol/l or \>148mmol/l serum potassium \<3.1 mmol/l or \>5.6 mmol/l.
14. Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times the upper limit of normal range within 6 months.
15. Current concomitant illness or physical impairment or mental condition that in the judgment of the investigator could interfere with the effective conduct of the trial or constitutes a significant risk to the participants' well-being.
16. Arm circumference that is too large (\>55 cm) or too small (\<15-24 cm) to allow accurate measurement of BP.
17. Currently taking or might need during the trial, a concomitant treatment which is known to interact with one or more of the trial medications: digoxin, lithium, diabetics receiving aliskiren, moderate and strong CYP3A4 inhibitors (e.g. ritonavir, ketoconazole, diltiazem\], simvastatin \>20 mg/day, immunosuppressants.
18. Might need treatment with drugs that are prohibited during the trial: other antihypertensive drugs, endothelin receptor antagonists, neprilysin inhibitors, or other drugs that may affect BP.
19. Current surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of trial drugs such as prior major gastrointestinal tract surgery (e.g. gastrectomy, lap band, or bowel resection) or acute flare of inflammatory bowel disease within one year.
20. Individuals working \>2 nightshifts per week.
21. Participated in any investigative drug or device trial within the previous 30 days.
22. History of alcohol or drug abuse within 12 months.
At randomization visit
1. Unable to adhere to the trial procedures during the run-in treatment period.
2. Any of the following which in the investigator's judgment may compromise the safety of the participant if randomized to the trial medications:
1. High or low clinic BP levels even in the light of the values for home BP that are available for that participant. The exact levels of BP are not specified, since there is clinical uncertainty as to the relevance of BP levels which are high or low in clinic only; for example, the clinical relevance of 'whitecoat hypertension' is uncertain.
2. High or low home diastolic BP (DBP) levels. The exact levels of DBP is not specified, reflecting clinical uncertainty of the implications of isolated diastolic hypertension. However, home DBP values of \>99 mmHg may typically be considered as requiring treatment intensification, and such participants would not be suitable for randomization.
3. Any abnormal laboratory value which in the judgment of the investigator could interfere with the effective conduct of the trial or constitutes a significant risk to the participants' well-being.
18 Years
ALL
No
Sponsors
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George Medicines PTY Limited
INDUSTRY
Responsible Party
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Principal Investigators
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Anthony Rodgers, Professor
Role: PRINCIPAL_INVESTIGATOR
The George Institute
Locations
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Elite Clinical Studies
Phoenix, Arizona, United States
Headlands Research
Scottsdale, Arizona, United States
Quality of Life Medical & Research Associates
Tucson, Arizona, United States
Valiance Clinical Research
South Gate, California, United States
Valiance Clinical Research
Tarzana, California, United States
Clinical Research of Brandon
Brandon, Florida, United States
Inpatient Research Clinic
Hialeah, Florida, United States
Multi-Speciality Research Associates
Lake City, Florida, United States
Suncoast Research Group
Miami, Florida, United States
New Horizon Research Center
Miami, Florida, United States
Ocala Research Institute
Ocala, Florida, United States
Suncoast Research Associates
St. Petersburg, Florida, United States
Accel Research
St. Petersburg, Florida, United States
Precision Research Center
Tampa, Florida, United States
Meridian Clinical Research
Savannah, Georgia, United States
Buckhead Primary Care Research
Snellville, Georgia, United States
Loyola University
Maywood, Illinois, United States
Meridian Clinical Research
Baton Rouge, Louisiana, United States
Meridian Clinical Research
Endwell, New York, United States
Javarra Research
Charlotte, North Carolina, United States
East Carolina University
Greenville, North Carolina, United States
The University of Tennessee Health Science Center
Memphis, Tennessee, United States
ACRC Trials - Southwest Medical Village
Austin, Texas, United States
ACRC Trials - Premier Family Physicians
Austin, Texas, United States
ACRC Trials - Family Medicine Associates of Texas
Carlton, Texas, United States
Synergy Groups Medical
Houston, Texas, United States
Synergy Groups Medical
Houston, Texas, United States
Synergy Groups Medical
Missouri City, Texas, United States
North Hills Medical Research
North Richland Hills, Texas, United States
ACRC Trials - Village Health Partners
Plano, Texas, United States
Meridian Clinical Research
Portsmouth, Virginia, United States
Castle Hill Medical Centre
Castle Hill, New South Wales, Australia
Princess Alexandra Hospital - Hypertension Unit
Brisbane, Queensland, Australia
Hudson Institute of Medical Research
Clayton, Victoria, Australia
Barwon Health, Geelong University Hospital
Geelong, Victoria, Australia
Curtin University
Bentley, Western Australia, Australia
Royal Perth Hospital
Perth, Western Australia, Australia
Private Cardiologic Ambulance, Medicus Services s.r.o
Brandýs nad Labem, Central Bohemia, Czechia
EDUMED, s.r.o
Broumov, Kralovehradsky, Czechia
EDUMED, s.r.o
Jaroměř, Kralovehradsky, Czechia
Middlemore Clinical Trials
Otahuhu, Auckland, New Zealand
Gisborne Hospital
Gisborne, , New Zealand
Medical University of Gdansk
Gdansk, Gdansk, Poland
Futuremeds
Wroclaw, Wroclaw, Poland
Medical University of Gdansk
Gdansk, , Poland
Pratia Katowice Medical Centre
Katowice, , Poland
Pratia Katowice Medical Centre
Katowice, , Poland
Nowodworskie Medical Center
Nowy Dwór Mazowiecki, , Poland
Medical Center Pratia Poznan
Poznan, , Poland
ETG Network
Skierniewice, , Poland
ETG Network
Skierniewice, , Poland
The Medical University of Warsaw
Warsaw, , Poland
EMC Instytut Medyczny S.A
Wroclaw, , Poland
Futuremeds
Wroclaw, , Poland
Clinical Medicine Academic & Research Centre
Colombo, , Sri Lanka
Institute of Cardiology, National Hospital of Sri Lanka
Colombo, , Sri Lanka
Colombo South Teaching Hospital
Dehiwala, , Sri Lanka
Karapitiya Teaching Hospital
Galle, , Sri Lanka
Jafna Teaching Hospital
Jaffna, , Sri Lanka
Kandy National Hospital
Kandy, , Sri Lanka
Kurunegala Teaching Hospital
Kurunegala, , Sri Lanka
Negombo District General Hospital
Negombo, , Sri Lanka
Sri Jayawardenapura General Hospital
Nugegoda, , Sri Lanka
Colombo North Teaching Hospital
Ragama, , Sri Lanka
Steploe Medical Centre
Soham, Cambridgeshire, United Kingdom
Ashfields Primary Care Centre
Sandbach, Cheshire, United Kingdom
Newquay Medical
Newquay, Cornwall, United Kingdom
Royal Primary care Ashgate
Chesterfield, Derbyshire, United Kingdom
Carmel Medical Practice
Darlington, Durham, United Kingdom
PRC Leciester
Leicester, East Midlands, United Kingdom
Portmill Surgery
Hitchin, Herts., United Kingdom
Layton Medical Centre
Blackpool, Lancashire, United Kingdom
Waterloo Medical Centre
Blackpool, Lancashire, United Kingdom
Burbage Surgery
Hinckley, Leicestershire, United Kingdom
Belmont Health Centre
Harrow, London, United Kingdom
The Adam Practice
Upton, Poole, United Kingdom
Heart of bath Medical Partnership
Bath, Somerset, United Kingdom
West Walk Surgery
Bristol, Somerset, United Kingdom
Tyntesfield Medical Group
Nailsea, Somerset, United Kingdom
Clifton Medical centre
Rotherham, South Yorkshire, United Kingdom
Ely Bridge
Cardiff, Wales, United Kingdom
Atherstone Surgery
Atherstone, Warwickshire, United Kingdom
Lakeside Surgery
Coventry, West Midlands, United Kingdom
Sherbourne Medical Centre
Royal Leamington Spa, West Midlands, United Kingdom
Hathaway Surgery
Chippenham, Wiltshire, United Kingdom
Rowden Surgery
Chippenham, Wiltshire, United Kingdom
Trowbridge Health Centre
Trowbridge, Wiltshire, United Kingdom
Bart's NHS Trust
London, , United Kingdom
Ecclesfield group Practice
Sheffield, , United Kingdom
Countries
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References
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Rodgers A, Salam A, Schutte AE, Cushman WC, de Silva HA, Di Tanna GL, Grobbee DE, Narkiewicz K, Ojji DB, Poulter NR, Schlaich MP, Oparil S, Spiering W, Williams B, Wright JT Jr, Lakshman P, Uluwattage W, Hay P, Pereira T, Amarasena N, Ranasinghe G, Gianacas C, Shanthakumar M, Liu X, Wang N, Gnanenthiran SR, Whelton PK; GMRx2 Investigators. Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial. Lancet. 2024 Oct 19;404(10462):1536-1546. doi: 10.1016/S0140-6736(24)01744-6.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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GMRx2-HTN-2020-ACT1
Identifier Type: -
Identifier Source: org_study_id
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