Efficacy and Safety of GMRx2 (a Single Pill Combination Containing Telmisartan/Amlodipine/Indapamide) Compared to Dual Combinations for the Treatment of Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,385
- 试验地点
- 78
- 主要终点
- Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12
研究概览
简要总结
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.
详细描述
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 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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):
- •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
- •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.
排除标准
- •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/1.73m
- •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 (<15-24 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.
- •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.
研究组 & 干预措施
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
干预措施: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg (Drug)
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
干预措施: telmisartan 40 mg/amlodipine 5 mg/indapamide 2.5 mg (Drug)
Dual - TA
Telmisartan 20 mg/amlodipine 2.5 mg . At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg
干预措施: Telmisartan 20 mg/amlodipine 2.5 mg (Drug)
Dual - TA
Telmisartan 20 mg/amlodipine 2.5 mg . At week 6 visit, forced up-titration to telmisartan 40 mg/amlodipine 5 mg
干预措施: telmisartan 40 mg/amlodipine 5 mg (Drug)
Dual - TI
Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg
干预措施: Telmisartan 20 mg/indapamide 1.25 mg (Drug)
Dual - TI
Telmisartan 20 mg/indapamide 1.25 mg. At week 6 visit, forced up-titration to telmisartan 40 mg/indapamide 2.5 mg
干预措施: telmisartan 40 mg/indapamide 2.5 mg (Drug)
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
干预措施: Amlodipine 2.5 mg/indapamide 1.25 mg (Drug)
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
干预措施: amlodipine 5 mg/indapamide 2.5 mg (Drug)
结局指标
主要结局
Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12
时间窗: 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.
次要结局
- 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 Systolic Blood Pressure (SBP) From Randomization to Week 12(Week 12)
- 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)
- Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <140 and Diastolic Blood Pressure (DBP) <90 mmHg at Week 6(Week 6)
- Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12(Week 12)
- Percentage of Participants With Clinic Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6(Week 6)
- Difference in Change in Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6(Week 6)
- Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 12(Week 12)
- Difference in Change in Home Seated Mean Diastolic Blood Pressure (DBP) From Randomization to Week 6(Week 6)
- Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 12(Week 12)
- Difference in Change in Trough Home Seated Mean Systolic Blood Pressure (SBP) From Randomization to Week 6(Week 6)
- Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 12(Week 12)
- Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <135 and Diastolic Blood Pressure (DBP) <85 mmHg at Week 6(Week 6)
- Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 12(Week 12)
- Percentage of Participants With Home Seated Mean Systolic Blood Pressure (SBP) <130 and Diastolic Blood Pressure (DBP) <80 mmHg at Week 6(Week 6)