Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001533381p
Ethics application status
Submitted, not yet approved
Date submitted
25/10/2017
Date registered
6/11/2017
Date last updated
14/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Combination low dose blood pressure lowering treatment for patients with untreated hypertension
Scientific title
Combination low dose blood pressure lowering treatment for patients with untreated hypertension: Evaluation of short-term safety.
Secondary ID [1] 293190 0
None
Universal Trial Number (UTN)
Trial acronym
TRIlogy
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 305188 0
Condition category
Condition code
Cardiovascular 304506 304506 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1
Ultra-low dose TEL/AML/IND: telmisartan (TEL 10 mg once daily, oral tablet), amlodipine (AML 1.25 mg once daily, oral tablet), and indapamide (IND 0.625 mg once daily oral tablet) for two weeks
Or
Arm 2
Standard-low -dose LOS/AML/HCT: losartan (LOS 25 mg once daily, oral tablet), amlodipine (AML 2.5 mg once daily, oral tablet), and hydrochlorothiazide (HCT 12.5 mg once daily, oral tablet) for four weeks.

Each drug will be administered via oral capsule once daily. Adherence will be monitored by drug tablet return and diary card completion.
Intervention code [1] 299445 0
Treatment: Drugs
Comparator / control treatment
The standard low dose is a comparison group for the purposes of this study.
Control group
Dose comparison

Outcomes
Primary outcome [1] 303744 0
The primary objective is to provide initial safety data on the short-term (2 weeks) safety of one ultra-low dose combination and another standard-low dose combination. Arm 1 will investigate ultra-low dose telmisartan (TEL 10 mg), amlodipine (AML 1.25 mg), and indapamide (IND 0.625 mg). Arm 2 will investigate standard-low dose losartan (LOS 25 mg), amlodipine (AML 2.5 mg), and hydrochlorothiazide (HCT 12.5 mg). Both arms will be monitored over a two-week period in patients with untreated hypertension.
Safety is defined as the absence of any of the following:
1. Systolic blood pressure less than 90 mm Hg and or diastolic blood pressure less than 60 mm Hg
2. Symptoms suggestive of hypotension (e.g. dizziness, light headedness)
3. Clinically significant changes in ECG
4. Clinically significant changes in blood biochemistry
5. Clinically significant changes in physical examination
6. Clinically significant changes in concomitant medications
7. Clinically significant adverse events
8. Any other clinical outcome for which there is a reasonable possibility that the drug caused the adverse event or suspected adverse event
Timepoint [1] 303744 0
Two weeks after randomisation. Adverse Events assessed at every visit through Adverse Events questioning and physical examinations (screening and End of Study visit). Symptoms are recorded daily in a diary card. Blood pressure (using Electronic sphygmomanometer) assessed at screening, randomisation and end of study visit. ECG performed at screening and end of study visit.
Amlodipine

Most Common: Headache, oedema
Common ( > 1.0%): Headache, fatigue, nausea, abdominal pain, drowsiness

Hydrochlorothiazide

Mild:Numbness / tingling in hands, muscle spasm, pains or cramps, restlessness, dizziness, headache, vomiting, nausea, loss of appetite, stomach cramps, diarrhea, constipation, fever, weakness, sore saliva glands
May be serious:Blurred vision, yellow vision, yellowing of skin and / or eyes, skin rash, severe stomach pain often with nausea or vomiting, increased sensitivity to sunlight, signs of anaemia such as tiredness, being short of breath when exercising, dizziness and looking pale, frequent infections such as fever, severe chills, sore throat or mouth ulcers, bleeding or bruising more easily than normal, nose bleeds, unusual bleeding or bruising under the skin, purple or red spots visible through the skin, signs of gout such as painful, swollen joints, fast heart beat, changes in the amount of urine pass (too little, none at all or large amounts) or the passing of red coloured urine, excessive thirst, dry mouth and skin
Serious: Coughing, difficulty breathing, wheezing, breathlessness which may be severe and usually worsens on lying down, sudden signs of allergy such as rash. Itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing, severe skin reaction starting with painful red areas, then large blisters and ending with peeling of layers of skin. This may be accompanied by fever and chills, aching muscles and generally feeling unwell. Pinkish, itchy swellings on the skin, also called hives or nettle rash.

Indapamide

< 1.0%: Drowsiness, sleepiness, insomnia, weakness, lethargy, visual disturbance, nausea / anorexia, dryness of mouth, gastralgia, vomiting, diarrhea, constipation, joint pain, back pain, weakness of legs, orthastatic hypotension, tachycardia, ECG changes, impotence, modification of libido, polyuria, rash, pruritus, gout, tinnitus, malaise / fainting, sweat
> 1% < 3%: Asthenia, headache, dizziness, vertigo, muscle cramps

Losartan

Common / Mild: Dizziness, lightheadedness, tiredness or weakness, spinning sensation, generally feeling unwell, increased sensitivity of the skin to sun, inability to get or maintain an erection, cough
Serious: Skin rash, itchiness, anemia, aching muscles not caused by exercise, bleeding or bruising more easily than normal
Very Serious: Severe and sudden onset of pinkish, itchy swellings on the skin, also called hives or nettle rash

Telmisartan

Serious: Dizziness or spinning sensation, fainting, tiredness or weakness, flu-like symptoms, pain in the chest, diarrhea, indigestion, stomach pain or discomfort, wind or discomfort, wind or excessive gas in the stomach or bowel (flatulence), upper respiratory tract infections, shortness of breath, back pain, aching muscles, not caused by exercise, muscle spasms or leg cramps, painful joints, tendon pain, urinary tract infections, trouble sleeping, feeling anxious, depression, fast or slow heart beats, visual disturbance, increased sweating, dry mouth, allergic skin reactions including skin rash, itchiness, redness of the skin, symptoms that may indicate low blood sugar levels in the blood, such as sweating, weakness, hunger, dizziness, trembling, headache or numbness, swelling of face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing, severe and sudden onset of itchy or raised skin rash, hives or nettle rash


The risks of a blood test include pain, a bruise at the point where the blood is taken, redness and swelling of the vein, infection, and a rare risk of fainting.
Secondary outcome [1] 340034 0
Change from baseline to Week 2 in systolic blood pressure
Timepoint [1] 340034 0
Two weeks after randomisation

Eligibility
Key inclusion criteria
1. Willing and able to provide written, informed consent;

2. Be male or female aged 18 years or over;

3. Have hypertension, defined as an in-office systolic blood pressure of more than 140 mm Hg and/or a diastolic blood pressure of more than 90 mmHg taken in triplicate, supine, after 5 minutes rest, taken over a 10-minute period. Patients may be untreated, newly diagnoses, or have previously been treated with an antihypertensive (but must have a two-week washout period from previous treatments);

4. Not be of childbearing potential, or agree to use contraception for the duration of the protocol (e.g. diaphragm, male condom, combined oral contraceptive pill, copper intrauterine device, levonorgestrel intrauterine system or etonogestrel implant). Note the partners of male participants must also use contraception for the duration of the protocol; and

5. Willing to comply with all study assessment and attend all visits.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have severe hypertension, defined as an in-office systolic blood pressure more than 180 mm Hg and/or a diastolic blood pressure more than 110 mm Hg on three consecutive measurements taken over a 10-minute period;

2. Have hypertension with a known secondary cause (e.g. primary aldosteronism);

3. Have a previously recorded intolerance to any angiotensin receptor blocker, calcium channel blocker, diuretic or sulphonamide;

4. Have received antihypertensive treatment within the last two weeks;

5. Have concomitant illness, physical impairment or mental condition which in the opinion of the Investigator could interfere with the conduct of the study including assessments

6. Have unstable cardiac disease;

7. Have severe kidney disease;

8. Have severe liver disease;

9. Be pregnant or breastfeeding;

10. Any other medical condition that the Investigator believes should preclude the patient’s participation in the study;

11. Have participates in another clinical trial within 30 days of dosing; or

12. Have inability or unwillingness to provide written informed consent.

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Open label
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This is a preliminary pilot study, and as such, no formal sample size calculation has been performed

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 297820 0
Commercial sector/Industry
Name [1] 297820 0
George Medicines (The George Institute)
Country [1] 297820 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
George Medicines
Address
Level 5, 1 King Street, Newtown NSW 2042
Country
Australia
Secondary sponsor category [1] 296861 0
None
Name [1] 296861 0
Address [1] 296861 0
Country [1] 296861 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 298874 0
Bellberry Limited
Ethics committee address [1] 298874 0
129 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 298874 0
Australia
Date submitted for ethics approval [1] 298874 0
15/11/2017
Approval date [1] 298874 0
Ethics approval number [1] 298874 0

Summary
Brief summary
This is a randomised, parallel, open-label study for patients with hypertension, conducted by George Medicines. Ethical approval has been sought in November 2017, shortly followed by regulatory acknowledgement.

This research project aims to understand whether a single pill containing 3 types of blood pressure lowering medications at quarter-standard doses will more effectively lower blood pressure and have fewer side effects compared to a standard dose of a single type of hypertensive medication.

This research project will assess two different pill combinations for the treatment of high blood pressure, they are:

• Ultra-low dose: telmisartan (10 mg), amlodipine (1.25 mg), and indapamide (0.625 mg)

• Low-dose: losartan (25 mg), amlodipine (2.5 mg), and hydrochlorothiazide (12.5 mg)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78518 0
Dr Charlotte Lemech
Address 78518 0
Scientia Clinical Research
Level 5, Bright Building
Corner High and Avoca Street
Randwick NSW 2031
Country 78518 0
Australia
Phone 78518 0
+61 2 9382 5807
Fax 78518 0
Email 78518 0
c.lemech@unsw.edu.au
Contact person for public queries
Name 78519 0
Miss Rebecca Ho
Address 78519 0
GeorgeClinical
Level 5, 1 King Street
Newtown NSW 2042
Country 78519 0
Australia
Phone 78519 0
+61 410 677 175
Fax 78519 0
Email 78519 0
rho@georgeclinical.com
Contact person for scientific queries
Name 78520 0
Miss Rebecca Ho
Address 78520 0
GeorgeClinical
Level 5, 1 King Street
Newtown NSW 2042
Country 78520 0
Australia
Phone 78520 0
+61 410 677 175
Fax 78520 0
Email 78520 0
rho@georgeclinical.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.