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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04518306




Registration number
NCT04518306
Ethics application status
Date submitted
15/08/2020
Date registered
19/08/2020

Titles & IDs
Public title
Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension
Scientific title
Efficacy and Safety of GMRx2 (a Single Pill Combination Containing Telmisartan/Amlodipine/Indapamide) Compared to Placebo for the Treatment of Hypertension
Secondary ID [1] 0 0
GMRx2-HTN-2020-PCT1
Universal Trial Number (UTN)
Trial acronym
GMRx2_PCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg
Treatment: Drugs - Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Treatment: Drugs - Placebo

Experimental: Triple ¼ (GMRx2) - Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg

Active comparator: Triple ½ (GMRx2) - Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg

Placebo comparator: Placebo - Placebo


Treatment: Drugs: Telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg
Oral tablets

Treatment: Drugs: Telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg
Oral tablets

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Difference in change in home seated SBP from baseline to Week 4
Timepoint [1] 0 0
4 weeks
Secondary outcome [1] 0 0
Difference in change in clinic seated mean SBP from baseline to Week 4
Timepoint [1] 0 0
4 weeks
Secondary outcome [2] 0 0
Difference in change in clinic seated mean DBP from baseline to Week 4
Timepoint [2] 0 0
4 weeks
Secondary outcome [3] 0 0
Percentage of participants with clinic seated mean SBP <140 and DBP <90 mmHg at Week 4
Timepoint [3] 0 0
4 weeks
Secondary outcome [4] 0 0
Percentage of participants with clinic seated mean SBP <130 and DBP <80 mmHg at Week 4
Timepoint [4] 0 0
4 weeks
Secondary outcome [5] 0 0
Difference in change in home seated mean DBP from baseline to Week 4
Timepoint [5] 0 0
4 weeks
Secondary outcome [6] 0 0
Difference in change in trough home seated mean SBP from baseline to week 4
Timepoint [6] 0 0
4 weeks
Secondary outcome [7] 0 0
Difference in change in trough home seated mean DBP from baseline to week 4
Timepoint [7] 0 0
4 weeks
Secondary outcome [8] 0 0
Percentage of participants with home seated mean SBP <135 and DBP <85 mmHg at Week 4
Timepoint [8] 0 0
4 weeks
Secondary outcome [9] 0 0
Percentage of participants with home seated mean SBP <130 and DBP <80 mmHg at Week 4
Timepoint [9] 0 0
4 weeks

Eligibility
Key inclusion criteria
Inclusion Criteria

At screening visit:

1. Provided signed consent to participate in the trial.
2. Adult aged =18 years.
3. Low calculated CV risk according to local guidelines such that pharmacological BP-lowering treatment is not mandatory: e.g. Pooled Cohorts Equation 10-years ASCVD risk <10% in the USA.
4. Likely diagnosis of hypertension, defined as one or more of:

* automated SBP at this clinic visit according to trial methods (see Appendix 2) of =130mmHg on no BP lowering medicines or =120mmHg on 1 BP lowering medicine that will be stopped at this visit, OR
* documentation in last 6 months of office SBP = 140 mmHg and/or DBP = 90mmHg on no BP lowering medicines or SBP = 130 mmHg and/or DBP = 85mmHg on 1 BP lowering medicine that will be stopped at this visit, OR
* documentation in last 6 months of home SBP = 130 mmHg and/or DBP = 80mmHg on no BP lowering medicines or SBP = 120 mmHg and/or DBP = 75mmHg on 1 BP lowering medicine that will be stopped at this visit, OR
* documentation in last 6 months of ambulatory daytime SBP = 130 mmHg and/or DBP = 80mmHg on no BP lowering medicines or SBP = 120 mmHg and/or DBP = 75mmHg on 1 BP lowering medicine that will be stopped at this visit
5. No contraindication to trial medications, including 2-weeks placebo run-in and 4-weeks randomized treatment period with GMRx2 (dose version 1 or 2) or placebo.

At randomization visit:

1. Home seated mean SBP 130-154 mmHg in the week before the randomization visit.
2. Adherence of 80-120% to placebo run-in.
3. Tolerated placebo run-in.
4. Adherence to home BP monitoring schedule: in the week before randomization, at least 6 measures (e.g. =2 sets of triplicate 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
At screening visit:

1. Receiving 2 or more BP-lowering drugs.
2. Clinic seated mean SBP =160 mmHg and/or DBP =100 mmHg.
3. 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.
4. 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).
5. Contraindication, including hypersensitivity (e.g. anaphylaxis or angioedema), to any of the 3 trial medications.
6. Current/history of transient ischemic attack, stroke, or hypertensive encephalopathy.
7. Current/history of acute coronary syndrome, unstable angina, myocardial infarction, percutaneous transluminal coronary revascularization, or coronary artery bypass graft.
8. Current/history of New York Heart Association class III and IV congestive heart failure.
9. Current/history of a known secondary cause of hypertension, such as primary aldosteronism, renal artery stenosis, pheochromocytoma, or Cushing's syndrome.
10. Current/history of substantially uncontrolled diabetes (HbA1c > 11.0%) within last three months.
11. Current/history of end-stage renal disease or anuria or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2.
12. Current/history of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper limit of normal range within 6 months.
13. 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.
14. Arm circumference that is too large (>55 cm) or too small (<20 cm) to allow accurate measurement of BP.
15. Currently taking or might need during the trial, a concomitant treatment which is known to interact significantly with the trial medication: digoxin, lithium, diabetics receiving aliskiren, moderate and strong CYP3A4 inhibitors [e.g. ritonavir, ketoconazole, diltiazem], simvastatin >20 mg/day, immunosuppressants.
16. 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 Error! Reference source not found.).
17. 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.
18. Individuals working >2-night shifts per week.
19. Participated in any investigational drug or device trial within the previous 30 days.
20. History of alcohol or drug abuse within 12 months.

At randomization visit:

1. Unable to adhere to the trial procedures during the run-in period.
2. Any of the following which in the investigator's judgment may compromise the safety of the participant if randomized to the trial medications:

1. 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/low in clinic only; for example the clinical relevance of 'whitecoat hypertension' is uncertain.
2. High or low home DBP levels. The exact levels of DBP are not specified, reflecting clinical uncertainty of for example 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.
3. 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.
4. Fulfilling any of the exclusion criteria mentioned for the screening visit, when verified again at randomization visit.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/10/2023
Sample size
Target
Accrual to date
Final
295
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Castle Hill Medical Centre - Castle Hill
Recruitment hospital [2] 0 0
Hudson Institute of Medical Research - Clayton
Recruitment hospital [3] 0 0
Barwon Health, Geelong University Hospital - Geelong
Recruitment hospital [4] 0 0
Curtin University - Bentley
Recruitment hospital [5] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2154 - Castle Hill
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment postcode(s) [4] 0 0
6102 - Bentley
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Nigeria
State/province [9] 0 0
Federal Capital Territory
Country [10] 0 0
Nigeria
State/province [10] 0 0
Kano
Country [11] 0 0
Sri Lanka
State/province [11] 0 0
Colombo
Country [12] 0 0
Sri Lanka
State/province [12] 0 0
Dehiwala
Country [13] 0 0
Sri Lanka
State/province [13] 0 0
Galle
Country [14] 0 0
Sri Lanka
State/province [14] 0 0
Jaffna
Country [15] 0 0
Sri Lanka
State/province [15] 0 0
Kandy
Country [16] 0 0
Sri Lanka
State/province [16] 0 0
Kurunegala
Country [17] 0 0
Sri Lanka
State/province [17] 0 0
Ragama
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Cambridgeshire
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Cornwall
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Leicestershire
Country [21] 0 0
United Kingdom
State/province [21] 0 0
London
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Somerset
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Surrey
Country [24] 0 0
United Kingdom
State/province [24] 0 0
West Midlands
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Wiltshire
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Romsey
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Wellingborough

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
George Medicines PTY Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anthony Rodgers, Professor
Address 0 0
The George Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No If the sponsor receives a request for study data, then such requests will be reviewed by sponsor following completion of regulatory submissions and review, and with support from members of the GMRX2 steering committee who will advise on the scientific merit and integrity of the proposed analysis.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04518306