Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension

NCT04518293 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: GMRx2-HTN-2020-ACT1
• Study Type: interventional
• Target: 1,385
• Locations: 7 countries
• Sites: 89

Brief Summary

Recent hypertension guidelines recommend combination therapy as initial treatment for many or most patients. Several trials suggest triple low-dose combination therapy may be highly effective in terms of achieving blood pressure (BP) control without increasing adverse effects. This trial is designed to investigate the efficacy and safety of GMRx2 in participants with high blood pressure compared to dual combinations.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12

  The primary outcome measure is difference in change in average home SBP for GMRx2 vs each dual combination evaluated from randomization to Week 12. The change in home SBP from randomization for all treatment arms was measured using least squares (LS) mean change. The pairwise comparisons between GMRx2 and dual treatments in change in home SBP were estimated using LS means difference and are described in the statistical analysis.

  Week 12

Secondary Outcomes (17)

• Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12

  Week 12

• Difference in Change in Clinic Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6

  Week 6

• Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12

  Week 12

• Difference in Change in Clinic Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6

  Week 6

• Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 12

  Week 12

Other Outcomes (22)

• Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 12

  Week 12

• Percentage of Participants Discontinued Trial Medication Due to Adverse Event (AE)/Serious Adverse Event (SAE) From Randomization to Week 6

  Week 6

• Percentage of Participants With a Serious Adverse Event (SAE) From Randomization to Week 12

  At Week 12

Study Arms (4)

GMRx2

EXPERIMENTAL

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

Drug: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg; Drug: telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg

Dual - TA

ACTIVE COMPARATOR

Telmisartan 20 mg/amlodipine 2.5 mg . At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg

Drug: Telmisartan 20 mg/amlodipine 2.5 mg; Drug: telmisartan 40 mg/amlodipine 5 mg

Dual - TI

ACTIVE COMPARATOR

Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg

Drug: Telmisartan 20 mg/indapamide 1.25 mg; Drug: telmisartan 40 mg/indapamide 2.5 mg

Dual - AI

ACTIVE COMPARATOR

Amlodipine 2.5 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to amlodipine 5 mg/indapamide 2.5 mg

Drug: Amlodipine 2.5 mg/indapamide 1.25 mg; Drug: amlodipine 5 mg/indapamide 2.5 mg

Interventions

Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg DRUG

Single pill

GMRx2

telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg DRUG

Single pill

GMRx2

Telmisartan 20 mg/amlodipine 2.5 mg DRUG

oral tablet

Dual - TA

telmisartan 40 mg/amlodipine 5 mg DRUG

oral tablet

Dual - TA

Telmisartan 20 mg/indapamide 1.25 mg DRUG

oral tablet

Dual - TI

telmisartan 40 mg/indapamide 2.5 mg DRUG

oral tablet

Dual - TI

Amlodipine 2.5 mg/indapamide 1.25 mg DRUG

oral tablet

Dual - AI

amlodipine 5 mg/indapamide 2.5 mg DRUG

oral tablet

Dual - AI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At screening visit
• Provided signed consent to participate in the trial.
• Adult of age ≥18 years.
• Attended automated clinic seated mean systolic blood pressure (SBP) (average of last 2 measurements calculated by the device):
• 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
• Home seated mean SBP 110-154 mmHg in the week prior to the randomization visit.
• Adherence of 80-120% to run-in medication.
• Tolerated run-in medication.
• 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.

You may not qualify if:

• At screening visit
• Receiving 4 or more BP-lowering drugs.
• Receiving any BP lowering drugs for indications other than hypertension e.g. heart failure
• 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.
• 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).
• 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.
• Current/history of transient ischemic attack, stroke, or hypertensive encephalopathy.
• Current/history of acute coronary syndrome, unstable angina, myocardial infarction, percutaneous transluminal coronary revascularization, or coronary artery bypass graft.
• 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.
• Current/history of New York Heart Association class III and IV congestive heart failure.
• Current/history of a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.
• Current/history of substantially uncontrolled diabetes (HbA1c \> 11.0%) within last three months.
• Current/history of end-stage renal disease or anuria or estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73m2.
• 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.
• Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times the upper limit of normal range within 6 months.

Sponsors & Collaborators

• George Medicines PTY Limited: lead

Study Sites (89)

Elite Clinical Studies

Phoenix, Arizona, 85018, United States

Location

Headlands Research

Scottsdale, Arizona, 85260, United States

Location

Quality of Life Medical & Research Associates

Tucson, Arizona, 85712, United States

Location

Valiance Clinical Research

South Gate, California, 90280, United States

Location

Valiance Clinical Research

Tarzana, California, 91356, United States

Location

Clinical Research of Brandon

Brandon, Florida, 33511, United States

Location

Inpatient Research Clinic

Hialeah, Florida, 33013, United States

Location

Multi-Speciality Research Associates

Lake City, Florida, 32055, United States

Location

Suncoast Research Group

Miami, Florida, 33135, United States

Location

New Horizon Research Center

Miami, Florida, 33165, United States

Location

Ocala Research Institute

Ocala, Florida, 34471, United States

Location

Suncoast Research Associates

St. Petersburg, Florida, 33173, United States

Location

Accel Research

St. Petersburg, Florida, 33709, United States

Location

Precision Research Center

Tampa, Florida, 33603, United States

Location

Meridian Clinical Research

Savannah, Georgia, 31406, United States

Location

Buckhead Primary Care Research

Snellville, Georgia, 30078, United States

Location

Loyola University

Maywood, Illinois, 60153, United States

Location

Meridian Clinical Research

Baton Rouge, Louisiana, 70809, United States

Location

Meridian Clinical Research

Endwell, New York, 13760, United States

Location

Javarra Research

Charlotte, North Carolina, 28210, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

The University of Tennessee Health Science Center

Memphis, Tennessee, 38105, United States

Location

ACRC Trials - Southwest Medical Village

Austin, Texas, 78735, United States

Location

ACRC Trials - Premier Family Physicians

Austin, Texas, 78746, United States

Location

ACRC Trials - Family Medicine Associates of Texas

Carlton, Texas, 75010, United States

Location

Synergy Groups Medical

Houston, Texas, 77036, United States

Location

Synergy Groups Medical

Houston, Texas, 77087, United States

Location

Synergy Groups Medical

Missouri City, Texas, 77459, United States

Location

North Hills Medical Research

North Richland Hills, Texas, 76180, United States

Location

ACRC Trials - Village Health Partners

Plano, Texas, 75093, United States

Location

Meridian Clinical Research

Portsmouth, Virginia, 23703, United States

Location

Castle Hill Medical Centre

Castle Hill, New South Wales, 2154, Australia

Location

Princess Alexandra Hospital - Hypertension Unit

Brisbane, Queensland, 4102, Australia

Location

Hudson Institute of Medical Research

Clayton, Victoria, 3168, Australia

Location

Barwon Health, Geelong University Hospital

Geelong, Victoria, 3220, Australia

Location

Curtin University

Bentley, Western Australia, 6102, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Private Cardiologic Ambulance, Medicus Services s.r.o

Brandýs nad Labem, Central Bohemia, 250 01, Czechia

Location

EDUMED, s.r.o

Broumov, Kralovehradsky, 550 01, Czechia

Location

EDUMED, s.r.o

Jaroměř, Kralovehradsky, 551 01, Czechia

Location

Middlemore Clinical Trials

Otahuhu, Auckland, 2025, New Zealand

Location

Gisborne Hospital

Gisborne, 4040, New Zealand

Location

Medical University of Gdansk

Gdansk, Gdansk, 80-214, Poland

Location

Futuremeds

Wroclaw, Wroclaw, 50-088, Poland

Location

Medical University of Gdansk

Gdansk, Poland

Location

Pratia Katowice Medical Centre

Katowice, 40-081, Poland

Location

Pratia Katowice Medical Centre

Katowice, Poland

Location

Nowodworskie Medical Center

Nowy Dwór Mazowiecki, Poland

Location

Medical Center Pratia Poznan

Poznan, Poland

Location

ETG Network

Skierniewice, 96-100, Poland

Location

ETG Network

Skierniewice, Poland

Location

The Medical University of Warsaw

Warsaw, Poland

Location

EMC Instytut Medyczny S.A

Wroclaw, Poland

Location

Futuremeds

Wroclaw, Poland

Location

Clinical Medicine Academic & Research Centre

Colombo, 10-01000, Sri Lanka

Location

Institute of Cardiology, National Hospital of Sri Lanka

Colombo, 10-01000, Sri Lanka

Location

Colombo South Teaching Hospital

Dehiwala, 10350, Sri Lanka

Location

Karapitiya Teaching Hospital

Galle, 80000, Sri Lanka

Location

Jafna Teaching Hospital

Jaffna, 40000, Sri Lanka

Location

Kandy National Hospital

Kandy, 20000, Sri Lanka

Location

Kurunegala Teaching Hospital

Kurunegala, 60000, Sri Lanka

Location

Negombo District General Hospital

Negombo, 11500, Sri Lanka

Location

Sri Jayawardenapura General Hospital

Nugegoda, 10250, Sri Lanka

Location

Colombo North Teaching Hospital

Ragama, 11010, Sri Lanka

Location

Steploe Medical Centre

Soham, Cambridgeshire, CB7 5JD, United Kingdom

Location

Ashfields Primary Care Centre

Sandbach, Cheshire, CW11 1EQ, United Kingdom

Location

Newquay Medical

Newquay, Cornwall, TR7 1RU, United Kingdom

Location

Royal Primary care Ashgate

Chesterfield, Derbyshire, S40 4AA, United Kingdom

Location

Carmel Medical Practice

Darlington, Durham, DL3 8SQ, United Kingdom

Location

PRC Leciester

Leicester, East Midlands, LE5 4PW, United Kingdom

Location

Portmill Surgery

Hitchin, Herts., SG49TH, United Kingdom

Location

Layton Medical Centre

Blackpool, Lancashire, FY3 7EN, United Kingdom

Location

Waterloo Medical Centre

Blackpool, Lancashire, FY4 3AD, United Kingdom

Location

Burbage Surgery

Hinckley, Leicestershire, LE10 2SE, United Kingdom

Location

Belmont Health Centre

Harrow, London, HA3 7LT, United Kingdom

Location

The Adam Practice

Upton, Poole, BH165PW, United Kingdom

Location

Heart of bath Medical Partnership

Bath, Somerset, BA2 3HT, United Kingdom

Location

West Walk Surgery

Bristol, Somerset, BS37 4AX, United Kingdom

Location

Tyntesfield Medical Group

Nailsea, Somerset, BS48 1BZ, United Kingdom

Location

Clifton Medical centre

Rotherham, South Yorkshire, S65 1DA, United Kingdom

Location

Ely Bridge

Cardiff, Wales, CV32 4RA, United Kingdom

Location

Atherstone Surgery

Atherstone, Warwickshire, CV9 1EU, United Kingdom

Location

Lakeside Surgery

Coventry, West Midlands, CV3 6NF, United Kingdom

Location

Sherbourne Medical Centre

Royal Leamington Spa, West Midlands, CV324RA, United Kingdom

Location

Hathaway Surgery

Chippenham, Wiltshire, SN14 6GT, United Kingdom

Location

Rowden Surgery

Chippenham, Wiltshire, SN15 2SB, United Kingdom

Location

Trowbridge Health Centre

Trowbridge, Wiltshire, BA14 8LW, United Kingdom

Location

Bart's NHS Trust

London, EC1M6BO, United Kingdom

Location

Ecclesfield group Practice

Sheffield, S35 9XQ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39426836 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Telmisartan; Amlodipine; Indapamide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Indoles

Limitations and Caveats

The trial included comparatively few participants with very high levels of blood pressure (BP), which makes direct comparison with previous trials challenging. The trial design did not allow a direct randomized comparison between ½ dose and standard dose combinations, or with other drugs and doses that are in common use. The option of non-uptitration after 6 weeks of half-dose regimens likely led to underestimation of the difference between standard dose regimens.

Results Point of Contact

• Title: Anthony Rogers (Principal Investigator)
• Organization: George Medicines Pty Limited

arodgers@georgeinstitute.org

+44-7983 578 290

Study Officials

• Anthony Rodgers, Professor

  The George Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: International, multicenter, randomized, double-blind, active-controlled, parallel group.

Study Record Dates

• First Submitted: August 15, 2020
• First Posted: August 19, 2020
• Study Start: July 9, 2021
• Primary Completion: August 11, 2023
• Study Completion: September 1, 2023
• Last Updated: June 3, 2025
• Results First Posted: June 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (31); CZ (3); SR (10); NZ (2); PL (12); GB (25); AU (6)