Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension
- Conditions
- Hypertension
- Interventions
- Registration Number
- NCT04518293
- Lead Sponsor
- George Medicines PTY Limited
- 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 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.
- Detailed Description
TRIAL DRUG:
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 the same time (± 2 hours) before home BP measurement is performed.
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 telmisartan20mg+amlodipine2.5mg, or telmisartan 20mg+indapamide 1.25mg, or amlodipine2.5mg+indapamide 1.25mg. At week 6 all doses will be doubled.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1385
At screening visit
- Provided signed consent to participate in the trial.
- Adult of age ≥18 years.
- Attended automated clinic seated mean SBP (average of last 2 measurements calculated by the device):
140-179 mmHg on 0 blood pressure (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: ≥3 days in the week before the randomization visit and ≥1 day per week during the preceding weeks, , with ≥2 measures in the specified morning and evening time periods on each day (i.e. accepting measures outside of the recommended 0600-1000 and 1800-2200 periods as long as they are in the am or pm, respectively).
At week 12 (for optional open-label extension)
- Provided signed informed consent.
- completed randomized treatment and willing to continue GMRx2-based regimen for up to 12 months.
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.
- 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.
- Arm circumference that is too large (>55 cm) or too small (<20 cm) to allow accurate measurement of BP.
- 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.
- 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 (see Appendix 5).
- 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.
- Individuals working >2 nightshifts per week.
- Participated in any investigative drug or device trial within the previous 30 days.
- History of alcohol or drug abuse within 12 months.
At randomization visit
-
Unable to adhere to the trial procedures during the run-in treatment period.
-
Any of the following which in the investigator's judgment may compromise the safety of the participant if randomized to the trial medications:
- 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.
- 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.
-
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.
-
Fulfilling any of the exclusion criteria mentioned for the screening visit, when verified again at randomization visit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dual - AI amlodipine 5 mg/indapamide 2.5 mg Amlodipine 2.5 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to amlodipine 5 mg/indapamide 2.5 mg Triple - TAI Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg 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 Triple - TAI telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg 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 Dual - TA Telmisartan 20 mg/amlodipine 2.5 mg . Telmisartan 20 mg/amlodipine 2.5 mg . At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg Dual - TA telmisartan 40 mg/amlodipine 5 mg Telmisartan 20 mg/amlodipine 2.5 mg . At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg Dual - TI telmisartan 40 mg/indapamide 2.5 mg Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg Dual - AI Amlodipine 2.5 mg/indapamide 1.25 mg Amlodipine 2.5 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to amlodipine 5 mg/indapamide 2.5 mg Dual - TI Telmisartan 20 mg/indapamide 1.25 mg Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg
- Primary Outcome Measures
Name Time Method Difference in change in home SBP from baseline to week 12 12 weeks
- Secondary Outcome Measures
Name Time Method Difference in change in clinic seated mean DBP from baseline to Week 12 12 weeks Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 6 6 weeks Difference in change in clinic seated mean SBP from baseline to Week 12 12 weeks Difference in change in clinic seated mean SBP from baseline to Week 6 6 weeks Difference in change in clinic seated mean DBP from baseline to Week 6 6 weeks Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 12 12 weeks Difference in change in home seated mean DBP from baseline to Week 12 12 weeks Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 6 6 weeks Difference in change in trough home seated mean SBP from baseline to week 12 12 weeks Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 12 12 weeks Difference in change in home seated mean SBP from baseline to Week 6 6 weeks Difference in change in home seated mean DBP from baseline to Week 6 6 weeks Difference in change in trough home seated mean SBP from baseline to Week 6 6 weeks Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 12 12 weeks Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 6 6 weeks Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 12 12 weeks Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 6 6 weeks
Trial Locations
- Locations (78)
Curtin University
🇦🇺Bentley, Western Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Karapitiya Teaching Hospital
🇱🇰Galle, Sri Lanka
Colombo North Teaching Hospital
🇱🇰Ragama, Sri Lanka
The Adam Practice
🇬🇧Upton, Poole, United Kingdom
Jafna Teaching Hospital
🇱🇰Jaffna, Sri Lanka
Ely Bridge
🇬🇧Cardiff, Wales, United Kingdom
Kandy National Hospital
🇱🇰Kandy, Sri Lanka
Negombo District General Hospital
🇱🇰Negombo, Sri Lanka
Sri Jayawardenapura General Hospital
🇱🇰Nugegoda, Sri Lanka
Elite Clinical Studies
🇺🇸Phoenix, Arizona, United States
Suncoast Research Group
🇺🇸Miami, Florida, United States
Meridian Clinical Research
🇺🇸Portsmouth, Virginia, United States
New Horizon Research Center
🇺🇸Miami, Florida, United States
Loyola University
🇺🇸Maywood, Illinois, United States
Multi-Speciality Research Associates
🇺🇸Lake City, Florida, United States
Ocala Research Institute
🇺🇸Ocala, Florida, United States
Inpatient Research Clinic
🇺🇸Hialeah, Florida, United States
Valiance Clinical Research
🇺🇸Tarzana, California, United States
Castle Hill Medical Centre
🇦🇺Castle Hill, New South Wales, Australia
Quality of Life Medical & Research Associates
🇺🇸Tucson, Arizona, United States
The University of Tennessee Health Science Center
🇺🇸Memphis, Tennessee, United States
Buckhead Primary Care Research
🇺🇸Snellville, Georgia, United States
Nowodworskie Medical Center
🇵🇱Nowy Dwór Mazowiecki, Poland
Medical Center Pratia Poznan
🇵🇱Poznań, Poland
Steploe Medical Centre
🇬🇧Soham, Cambridgeshire, United Kingdom
Kurunegala Teaching Hospital
🇱🇰Kurunegala, Sri Lanka
ACRC Trials - Village Health Partners
🇺🇸Plano, Texas, United States
Princess Alexandra Hospital - Hypertension Unit
🇦🇺Brisbane, Queensland, Australia
Medical University of Gdansk
🇵🇱Gdańsk, Poland
Futuremeds
🇵🇱Wrocław, Poland
EMC Instytut Medyczny S.A
🇵🇱Wrocław, Poland
Colombo South Teaching Hospital
🇱🇰Dehiwala, Sri Lanka
ACRC Trials - Family Medicine Associates of Texas
🇺🇸Carlton, Texas, United States
Ashfields Primary Care Centre
🇬🇧Sandbach, Cheshire, United Kingdom
Javarra Research
🇺🇸Charlotte, North Carolina, United States
North Hills Medical Research
🇺🇸North Richland Hills, Texas, United States
EDUMED, s.r.o
🇨🇿Jaroměř, Kralovehradsky, Czechia
Clinical Medicine Academic & Research Centre
🇱🇰Colombo, Sri Lanka
Synergy Groups Medical
🇺🇸Missouri City, Texas, United States
ETG Network
🇵🇱Skierniewice, Poland
The Medical University of Warsaw
🇵🇱Warsaw, Poland
Tyntesfield Medical Group
🇬🇧Nailsea, Somerset, United Kingdom
Belmont Health Centre
🇬🇧Harrow, London, United Kingdom
Clifton Medical centre
🇬🇧Rotherham, South Yorkshire, United Kingdom
Sherbourne Medical Centre
🇬🇧Leamington Spa, West Midlands, United Kingdom
Atherstone Surgery
🇬🇧Atherstone, Warwickshire, United Kingdom
Layton Medical Centre
🇬🇧Blackpool, Lancashire, United Kingdom
Bart's NHS Trust
🇬🇧London, United Kingdom
Trowbridge Health Centre
🇬🇧Trowbridge, Wiltshire, United Kingdom
Precision Research Center
🇺🇸Tampa, Florida, United States
ACRC Trials - Southwest Medical Village
🇺🇸Austin, Texas, United States
ACRC Trials - Premier Family Physicians
🇺🇸Austin, Texas, United States
Private Cardiologic Ambulance, Medicus Services s.r.o
🇨🇿Brandýs Nad Labem, Stredocesky, Czechia
Hudson Institute of Medical Research
🇦🇺Clayton, Victoria, Australia
Gisborne Hospital
🇳🇿Gisborne, New Zealand
Barwon Health, Geelong University Hospital
🇦🇺Geelong, Victoria, Australia
Institute of Cardiology, National Hospital of Sri Lanka
🇱🇰Colombo, Sri Lanka
Carmel Medical Practice
🇬🇧Darlington, Durham, United Kingdom
Newquay Medical
🇬🇧Newquay, Cornwall, United Kingdom
Royal Primary care Ashgate
🇬🇧Chesterfield, Derbyshire, United Kingdom
Portmill Surgery
🇬🇧Hitchin, Herts., United Kingdom
Waterloo Medical Centre
🇬🇧Blackpool, Lancashire, United Kingdom
PRC Leciester
🇬🇧Leicester, East Midlands, United Kingdom
Burbage Surgery
🇬🇧Hinckley, Leicestershire, United Kingdom
Lakeside Surgery
🇬🇧Coventry, West Midlands, United Kingdom
Ecclesfield group Practice
🇬🇧Sheffield, United Kingdom
Hathaway Surgery
🇬🇧Chippenham, Wiltshire, United Kingdom
Rowden Surgery
🇬🇧Chippenham, Wiltshire, United Kingdom
Headlands Research
🇺🇸Scottsdale, Arizona, United States
Clinical Research of Brandon
🇺🇸Brandon, Florida, United States
Suncoast Research Associates
🇺🇸Saint Petersburg, Florida, United States
Accel Research
🇺🇸Saint Petersburg, Florida, United States
Middlemore Clinical Trials
🇳🇿Otahuhu, Auckland, New Zealand
Pratia Katowice Medical Centre
🇵🇱Katowice, Poland
East Carolina University
🇺🇸Greenville, North Carolina, United States
Heart of bath Medical Partnership
🇬🇧Bath, Somerset, United Kingdom
West Walk Surgery
🇬🇧Bristol, Somerset, United Kingdom