GMRx2_ACT: Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Triple - TAI 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
Single pill
Drug: telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg
Signle pill
|
Active Comparator: Dual - TA 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 .
oral tablet
Drug: telmisartan 40 mg/amlodipine 5 mg
oral tablet
|
Active Comparator: Dual - TI 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
oral tablet
Drug: telmisartan 40 mg/indapamide 2.5 mg
oral tablet
|
Active Comparator: 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 |
Drug: Amlodipine 2.5 mg/indapamide 1.25 mg
oral tablet
Drug: amlodipine 5 mg/indapamide 2.5 mg
oral tablet
|
Outcome Measures
Primary Outcome Measures
- Difference in change in home SBP from baseline to week 12 [12 weeks]
Secondary Outcome Measures
- 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 12 [12 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]
- Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 6 [6 weeks]
- Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at 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 home seated mean SBP from baseline to Week 6 [6 weeks]
- Difference in change in home seated mean DBP from baseline to Week 12 [12 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 12 [12 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]
Other Outcome Measures
- Safety Outcomes [12 weeks]
Percentage of participants discontinued trial medication due to AE/SAE from baseline to week 12
- Safety Outcomes [6 weeks]
Percentage of participants discontinued trial medication due to AE/SAE from baseline to Week 6
- Safety Outcomes [12 weeks]
Percentage of participants with an SAE from baseline to Week 12
- Safety Outcomes [6 weeks]
Percentage of participants with SAE from baseline to Week 6
- Safety Outcomes [12 weeks]
Percentage of participants with symptomatic hypotension from baseline to Week 12
- Safety Outcomes [6 weeks]
Percentage of participants with symptomatic hypotension from baseline to Week 6
- Safety Outcomes [12 weeks]
Percentage of participants with serum sodium concentration below 135 mmol/l at Week 12
- Safety Outcomes [6 weeks]
Percentage of participants with serum sodium concentration below 135 mmol/l at Week 6
- Safety Outcomes [12 weeks]
Percentage of participants with serum sodium concentration above 145 mmol/l at Week 12
- Safety Outcomes [6 weeks]
Percentage of participants with serum sodium concentration above 145 mmol/l at Week 6
- Safety Outcomes [12 weeks]
Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 12
- Safety Outcomes [6 weeks]
Percentage of participants with serum potassium concentration below 3.5 mmol/l at Week 6
- Safety Outcomes [12 weeks]
Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 12
- Safety Outcomes [6 weeks]
Percentage of participants with serum potassium concentration above 5.5 mmol/l at Week 6
- Safety Outcomes [12 weeks]
Percentage of participants with eGFR drop of over 30% from baseline to Week 12
- Safety Outcomes [6 weeks]
Percentage of participants with eGFR drop of over 30% from baseline to Week 6
Eligibility Criteria
Criteria
Inclusion Criteria:
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):
150-179 mmHg on 0 blood pressure (BP)-lowering drugs, or 140-170 mmHg on 1 BP-lowering drug, or 130-160 mmHg on 2 BP-lowering drugs, or 120-150 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.
Exclusion Criteria:
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.
At week 12 (for optional open-label extension)
- contraindication to open-label GMRx2-ased BP-lowering treatment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Elite Clinical Studies | Phoenix | Arizona | United States | 85018 |
2 | Healthlines Research | Scottsdale | Arizona | United States | 85260 |
3 | Quality of Life Medical & Research Associates | Tucson | Arizona | United States | 85712 |
4 | Valiance Clinical Research | S. Gate | California | United States | 90280 |
5 | Valiance Clinical Research | Tarzana | California | United States | 91356 |
6 | Clinical Research of Brandon | Brandon | Florida | United States | 33511 |
7 | Inpatient Research Clinic | Hialeah | Florida | United States | 33013 |
8 | Multi-Speciality Research Associates | Lake City | Florida | United States | 32055 |
9 | Suncoast Research Group | Miami | Florida | United States | 33135 |
10 | New Horizon Research Center | Miami | Florida | United States | 33165 |
11 | Ocala Research Institute | Ocala | Florida | United States | 34471 |
12 | Suncoast Research Associates | Saint Petersburg | Florida | United States | 33173 |
13 | Accel Research | Saint Petersburg | Florida | United States | 33709 |
14 | Precision Research Center | Tampa | Florida | United States | 33603 |
15 | Meridian Clinical Research | Savannah | Georgia | United States | 31406 |
16 | Buckhead Primary Care Research | Snellville | Georgia | United States | 30078 |
17 | Loyola University | Maywood | Illinois | United States | 60153 |
18 | Meridian Clinical Research | Baton Rouge | Louisiana | United States | 70809 |
19 | Meridian Clinical Research | Endwell | New York | United States | 13760 |
20 | Javarra Research | Charlotte | North Carolina | United States | 28210 |
21 | East Carolina University | Greenville | North Carolina | United States | 27834 |
22 | The University of Tennessee Health Science Center | Memphis | Tennessee | United States | 38105 |
23 | ACRC Trials - Southwest Medical Village | Austin | Texas | United States | 78735 |
24 | ACRC Trials - Premier Family Physicians | Austin | Texas | United States | 78746 |
25 | ACRC Trials - Family Medicine Associates of Texas | Carlton | Texas | United States | 75010 |
26 | Synergy Groups Medical | Houston | Texas | United States | 77036 |
27 | Synergy Groups Medical | Houston | Texas | United States | 77087 |
28 | Synergy Groups Medical | Missouri City | Texas | United States | 77459 |
29 | North Hills Medical Research | North Richland Hills | Texas | United States | 76180 |
30 | ACRC Trials - Village Health Partners | Plano | Texas | United States | 75093 |
31 | Meridian Clinical Research | Portsmouth | Virginia | United States | 23703 |
32 | Castle Hill Medical Centre | Castle Hill | New South Wales | Australia | 2154 |
33 | Princess Alexandra Hospital - Hypertension Unit | Brisbane | Queensland | Australia | 4102 |
34 | Hudson Institute of Medical Research | Clayton | Victoria | Australia | 3168 |
35 | Barwon Health, Geelong University Hospital | Geelong | Victoria | Australia | 3220 |
36 | Curtin University | Bentley | Western Australia | Australia | 6102 |
37 | Royal Perth Hospital | Perth | Western Australia | Australia | 6000 |
38 | EDUMED, s.r.o | Broumov | Kralovehradsky | Czechia | 550 01 |
39 | EDUMED, s.r.o | Jaroměř | Kralovehradsky | Czechia | 551 01 |
40 | Private Cardiologic Ambulance, Medicus Services s.r.o | Brandýs Nad Labem | Stredocesky | Czechia | 250 01 |
41 | Middlemore Clinical Trials | Otahuhu | Auckland | New Zealand | 2025 |
42 | Gisborne Hospital | Gisborne | New Zealand | 4040 | |
43 | Medical University of Gdansk | Gdańsk | Gdansk | Poland | 80-214 |
44 | Futuremeds | Wrocław | Wroclaw | Poland | 50-088 |
45 | Pratia Katowice Medical Centre | Katowice | Poland | 40-081 | |
46 | ETG Network | Skierniewice | Poland | 96-100 | |
47 | Clinical Medicine Academic & Research Centre | Colombo | Sri Lanka | 10-01000 | |
48 | Clinical Medicine Academic & Research Centre | Colombo | Sri Lanka | 10-01000 | |
49 | Institute of Cardiology, National Hospital of Sri Lanka | Colombo | Sri Lanka | 10-01000 | |
50 | Institute of Cardiology, National Hospital of Sri Lanka | Colombo | Sri Lanka | 10-01000 | |
51 | Institute of Cardiology, National Hospital of Sri Lanka | Colombo | Sri Lanka | 10-01000 | |
52 | Institute of Cardiology, National Hospital of Sri Lanka | Colombo | Sri Lanka | 10-01000 | |
53 | Colombo South Teaching Hospital | Dehiwala | Sri Lanka | 10350 | |
54 | Karapitiya Teaching Hospital | Galle | Sri Lanka | 80000 | |
55 | Jafna Teaching Hospital | Jaffna | Sri Lanka | 40000 | |
56 | Kandy National Hospital | Kandy | Sri Lanka | 20000 | |
57 | Kurunegala Teaching Hospital | Kurunegala | Sri Lanka | 60000 | |
58 | Negombo District General Hospital | Negombo | Sri Lanka | 11500 | |
59 | Sri Jayawardenapura General Hospital | Nugegoda | Sri Lanka | 10250 | |
60 | Colombo North Teaching Hospital | Ragama | Sri Lanka | 11010 | |
61 | Steploe Medical Centre | Soham | Cambridgeshire | United Kingdom | CB7 5JD |
62 | Ashfields Primary Care Centre | Sandbach | Cheshire | United Kingdom | CW11 1EQ |
63 | Newquay Medical | Newquay | Cornwall | United Kingdom | TR7 1RU |
64 | Royal Primary care Ashgate | Chesterfield | Derbyshire | United Kingdom | S40 4AA |
65 | Carmel Medical Practice | Darlington | Durham | United Kingdom | DL3 8SQ |
66 | PRC Leciester | Leicester | East Midlands | United Kingdom | LE5 4PW |
67 | Portmill Surgery | Hitchin | Herts. | United Kingdom | SG49TH |
68 | Layton Medical Centre | Blackpool | Lancashire | United Kingdom | FY3 7EN |
69 | Waterloo Medical Centre | Blackpool | Lancashire | United Kingdom | FY4 3AD |
70 | Burbage Surgery | Hinckley | Leicestershire | United Kingdom | LE10 2SE |
71 | Belmont Health Centre | Harrow | London | United Kingdom | HA3 7LT |
72 | The Adam Practice | Upton | Poole | United Kingdom | BH165PW |
73 | Heart of bath Medical Partnership | Bath | Somerset | United Kingdom | BA2 3HT |
74 | West Walk Surgery | Bristol | Somerset | United Kingdom | BS37 4AX |
75 | Tyntesfield Medical Group | Nailsea | Somerset | United Kingdom | BS48 1BZ |
76 | Clifton Medical centre | Rotherham | South Yorkshire | United Kingdom | S65 1DA |
77 | Ely Bridge | Cardiff | Wales | United Kingdom | CV32 4RA |
78 | Atherstone Surgery | Atherstone | Warwickshire | United Kingdom | CV9 1EU |
79 | Lakeside Surgery | Coventry | West Midlands | United Kingdom | CV3 6NF |
80 | Sherbourne Medical Centre | Leamington Spa | West Midlands | United Kingdom | CV324RA |
81 | Hathaway Surgery | Chippenham | Wiltshire | United Kingdom | SN14 6GT |
82 | Rowden Surgery | Chippenham | Wiltshire | United Kingdom | SN15 2SB |
83 | Trowbridge Health Centre | Trowbridge | Wiltshire | United Kingdom | BA14 8LW |
84 | Bart's NHS Trust | London | United Kingdom | EC1M6BO | |
85 | Ecclesfield group Practice | Sheffield | United Kingdom | S35 9XQ |
Sponsors and Collaborators
- George Medicines PTY Limited
Investigators
- Principal Investigator: Anthony Rodgers, Professor, The George Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GMRx2-HTN-2020-ACT1