Efficacy and safety of GMRx2 (a single pill combination containing telmisartan/amlodipine/indapamide) compared to dual combinations for the treatment of hypertension: An international, multi-center, randomized, double-blind, active-controlled, parallel-group trial.

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: Not specified

Inclusion Criteria

At screening visit
1.Adults of age ?18 years (both male and female)
2.Clinic SBP: 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
1.Home seated mean SBP 120-154 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: ?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.

Exclusion Criteria

At screening visit
1.Receiving 4 or more BP-lowering drugs.
2.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.
3.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).
4.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.
5.Current/history of transient ischemic attack, stroke, or hypertensive encephalopathy.
6.Current/history of acute coronary syndrome, unstable angina, myocardial infarction, percutaneous transluminal coronary revascularization, or coronary artery bypass graft.
7.Current/history of New York Heart Association class III and IV congestive heart failure.
8.Current/history of a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.
9.Current/history of substantially uncontrolled diabetes (HbA1c > 11.0%) within last three months.
10.Current/history of end-stage renal disease or anuria or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2.
11.Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper limit of normal range within 6 months.
12.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.
13.Arm circumference that is too large (>55 cm) or too small (<20 cm) to allow accurate measurement of BP.
14.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.
15.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).
16.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.
17.Individuals working >2 nightshifts per week.
18.Participated in any investigative drug or device trial within the previous 30 days.
19.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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Difference in change in home SBP [0 and at 12 Weeks ]<br>Percentage of participants discontinued trial medication due to an Adverse Event (AE) or a Serious Adverse Event (SAE) [ 0 and at 12 Weeks ]<br>

Secondary Outcome Measures