Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
UNKNOWN
Clinical Phase
PHASE4
Total Enrollment
348 participants
Study Classification
INTERVENTIONAL
Study Start Date
2009-05-31
Study Completion Date
2015-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
This study was recommended by NICE, as part of its 2006 guidance for the treatment of hypertension, and is urgently required to provide evidence for the treatment recommendations in patients with resistant hypertension. The study will be a randomised placebo-controlled double-blind crossover comparison of an α-blocker (α), β-blocker (β), and K+-sparing diuretic (∆).
Patients will have a BP at entry above target on ABPM or home monitoring despite supervised administration of maximum tolerated doses of A+C+D. Over 48 weeks they will then receive, in random order either placebo or two doses each of doxazosin (α), bisoprolol (β) or spironolactone (∆). Each treatment cycle will last 12 weeks, with a forced dose-doubling at 6 weeks.
The time course for the study will be similar to study one. 340 patients will provide 90% power, at α=0.01 to detect a 3 mmHg overall difference in home sBP between any one drug and placebo, with spironolactone hypothesized to be best overall. The study will be able to detect a 6 mmHg difference in sBP between each subject's best and second-best drug predicted by tertile of plasma renin, justifying routine use of the measurement in patients with resistant hypertension.
Patients will have a BP at entry above target on ABPM or home monitoring despite supervised administration of maximum tolerated doses of A+C+D. Over 48 weeks they will then receive, in random order either placebo or two doses each of doxazosin (α), bisoprolol (β) or spironolactone (∆). Each treatment cycle will last 12 weeks, with a forced dose-doubling at 6 weeks.
The time course for the study will be similar to study one. 340 patients will provide 90% power, at α=0.01 to detect a 3 mmHg overall difference in home sBP between any one drug and placebo, with spironolactone hypothesized to be best overall. The study will be able to detect a 6 mmHg difference in sBP between each subject's best and second-best drug predicted by tertile of plasma renin, justifying routine use of the measurement in patients with resistant hypertension.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Effects of Combination Therapy With Alpha-1 Blocker (Bunazosin or Doxazosin) in the Treatment of Patients With Mild to Moderate Essential Hypertension
NCT00130156
High Blood Pressure
COMPLETED
PHASE4
Efficacy and Safety of Valsartan/Amlodipine Combination in Patients With Severe Hypertension
NCT00171535
Hypertension
COMPLETED
PHASE3
A Clinical Study to Compare Long-term Efficacy and Safety of an Aliskiren Based Regimen to a Hydrochlorothiazidebased Treatment Regimen With Optional Addition of Amlodipine
NCT00219154
Hypertension
COMPLETED
PHASE3
A Study Of Different Doses Of TBC3711 In Patients With Uncontrolled High Blood Pressure Already Taking Medications For High Blood Pressure.
NCT00272961
Resistant Hypertension
TERMINATED
PHASE2
A Study to Investigate the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension
NCT06168409
Resistant Hypertension
COMPLETED
PHASE3
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
In published surveys throughout the world the majority of patients with hypertension do not achieve target blood pressure. According to most guidelines including NICE, target blood pressure is 130/80 mmHg in patients with diabetes, 140/90 mmHg in other patients. In the UK there are currently at least 3 million people with treated hypertension whose blood pressure is not controlled. A significant number of these patients will have drug resistant hypertension, defined as:
"a blood pressure that is not adequately controlled to recommended treatment targets despite treatment with maximal recommended and tolerated doses of 3 drugs according to the current BHS/NICE guidelines and treatment algorithm, i.e. (\*ACE-inhibitor or \*ARB or direct renin inhibitor + \*CCB + Diuretic (any diuretic except spironolactone), i.e. A+C+D)".
(\*where ACE-inhibitor=angiotensin converting enzyme inhibitor, ARB=angiotensin receptor blocker, CCB=calcium channel blocker)
The causes of treatment resistance are unknown, and the choice of fourth-line drug almost entirely empirical. At present there is little comparative data for available drugs. There is considerable evidence pointing to Na+ retention as a common culprit, and some data supporting additional diuretics, or alpha blockade in resistant hypertension, though mainly added to two rather than three drugs.20,29,30 A retrospective analysis of two-drug combinations in trials reported that it makes no difference what is combined with what. 31 However, this conclusion conflicts with the view that drugs for hypertension fall into two main categories, acting respectively on the renin and volume components of hypertension, and that most benefit can be derived from combining drugs from different categories.10,32
Despite the successful adoption of the BHS/NICE treatment algorithm for the treatment of hypertension, there remains substantial clinical uncertainty about the preferred clinical management of people with drug resistant hypertension. This is an important question because such patients are at the highest risk for cardiovascular events. The current guidelines acknowledge that there is currently no adequate clinical trial evidence upon which to base recommendations for the preferred 4th line drug treatment for those with resistant hypertension.
It is possible that it makes no difference what drug is added as fourth-line treatment and that the response, on average, will be the same for all classes. Alternatively, it is also possible that one class of drug will always be superior to all the others because the mechanism underpinning resistant hypertension is common to all patients. In this regard, a popular view is that resistant hypertension is invariably due to excessive sodium retention and thus "further diuretic therapy" will always be the most effective treatment. A third possibility is that resistant hypertension is a heterogeneous state and that the study of average responses in cohorts in clinical studies masks substantial individual patient differences.
With regard to this, this study will address the hypothesis that the renin status of the patient defines the response to 4th line treatment in resistant hypertension, i.e. that low renin predicts sodium retention and the best response to diuretic therapy, whereas high renin predicts a better response to drugs that suppress renin, i.e. a β-blocker.
Hypothesis and Novel Aspects of the Trial
The primary hypothesis of the study is that the commonest cause of resistant hypertension is excessive Na+-retention, and that further diuretic therapy (spironolactone used in this study) will be superior to other potential "add-on drugs" for people with inadequate blood pressure control despite treatment with optimal or highest tolerated doses of the three drug classes recommended by the BHS/NICE treatment algorithm, i.e. A+C+D.
The main secondary objective is to use plasma renin measurements to evaluate an 'α, β, ∆' rule for the selection of the 4th line drug for patients with drug resistant hypertension - where α represents α-blockade, β represents β-blockade and ∆ represents "further diuretic therapy" as cited above. The main secondary hypothesis states that plasma renin (measured on a background of 3 drugs, i.e. A+C+D), will predict the most effective 4th line drug. We propose that:
α-blockade will be the most effective 4th line drug at lowering BP in patients in the mid-tertile of plasma renin, expected to be ≥20mU/L but \<100mU/L; β-blockade will be the most effective drug when renin is in the top tertile (expected to be ≥100Mu/L) as the drug blocks renin secretion; Further diuretic therapy with spironolactone will be most effective when plasma renin is in the lowest tertile (expected to be \<20mU/L), indicative of excessive sodium retention.
The study will also evaluate whether the routine use of plasma renin to predict best treatment in individual patients with resistant hypertension will be more cost-effective than using further diuretic therapy indiscriminately as the preferred 4th line drug for all patients.
Finally the study will investigate whether non-invasive assessment of haemodynamic parameters indicative of sodium retention and volume status, i.e. cardiac output, peripheral resistance and bioimpedance, can be used to predict the response to each drug in the α, β, ∆ sequence.
"a blood pressure that is not adequately controlled to recommended treatment targets despite treatment with maximal recommended and tolerated doses of 3 drugs according to the current BHS/NICE guidelines and treatment algorithm, i.e. (\*ACE-inhibitor or \*ARB or direct renin inhibitor + \*CCB + Diuretic (any diuretic except spironolactone), i.e. A+C+D)".
(\*where ACE-inhibitor=angiotensin converting enzyme inhibitor, ARB=angiotensin receptor blocker, CCB=calcium channel blocker)
The causes of treatment resistance are unknown, and the choice of fourth-line drug almost entirely empirical. At present there is little comparative data for available drugs. There is considerable evidence pointing to Na+ retention as a common culprit, and some data supporting additional diuretics, or alpha blockade in resistant hypertension, though mainly added to two rather than three drugs.20,29,30 A retrospective analysis of two-drug combinations in trials reported that it makes no difference what is combined with what. 31 However, this conclusion conflicts with the view that drugs for hypertension fall into two main categories, acting respectively on the renin and volume components of hypertension, and that most benefit can be derived from combining drugs from different categories.10,32
Despite the successful adoption of the BHS/NICE treatment algorithm for the treatment of hypertension, there remains substantial clinical uncertainty about the preferred clinical management of people with drug resistant hypertension. This is an important question because such patients are at the highest risk for cardiovascular events. The current guidelines acknowledge that there is currently no adequate clinical trial evidence upon which to base recommendations for the preferred 4th line drug treatment for those with resistant hypertension.
It is possible that it makes no difference what drug is added as fourth-line treatment and that the response, on average, will be the same for all classes. Alternatively, it is also possible that one class of drug will always be superior to all the others because the mechanism underpinning resistant hypertension is common to all patients. In this regard, a popular view is that resistant hypertension is invariably due to excessive sodium retention and thus "further diuretic therapy" will always be the most effective treatment. A third possibility is that resistant hypertension is a heterogeneous state and that the study of average responses in cohorts in clinical studies masks substantial individual patient differences.
With regard to this, this study will address the hypothesis that the renin status of the patient defines the response to 4th line treatment in resistant hypertension, i.e. that low renin predicts sodium retention and the best response to diuretic therapy, whereas high renin predicts a better response to drugs that suppress renin, i.e. a β-blocker.
Hypothesis and Novel Aspects of the Trial
The primary hypothesis of the study is that the commonest cause of resistant hypertension is excessive Na+-retention, and that further diuretic therapy (spironolactone used in this study) will be superior to other potential "add-on drugs" for people with inadequate blood pressure control despite treatment with optimal or highest tolerated doses of the three drug classes recommended by the BHS/NICE treatment algorithm, i.e. A+C+D.
The main secondary objective is to use plasma renin measurements to evaluate an 'α, β, ∆' rule for the selection of the 4th line drug for patients with drug resistant hypertension - where α represents α-blockade, β represents β-blockade and ∆ represents "further diuretic therapy" as cited above. The main secondary hypothesis states that plasma renin (measured on a background of 3 drugs, i.e. A+C+D), will predict the most effective 4th line drug. We propose that:
α-blockade will be the most effective 4th line drug at lowering BP in patients in the mid-tertile of plasma renin, expected to be ≥20mU/L but \<100mU/L; β-blockade will be the most effective drug when renin is in the top tertile (expected to be ≥100Mu/L) as the drug blocks renin secretion; Further diuretic therapy with spironolactone will be most effective when plasma renin is in the lowest tertile (expected to be \<20mU/L), indicative of excessive sodium retention.
The study will also evaluate whether the routine use of plasma renin to predict best treatment in individual patients with resistant hypertension will be more cost-effective than using further diuretic therapy indiscriminately as the preferred 4th line drug for all patients.
Finally the study will investigate whether non-invasive assessment of haemodynamic parameters indicative of sodium retention and volume status, i.e. cardiac output, peripheral resistance and bioimpedance, can be used to predict the response to each drug in the α, β, ∆ sequence.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Hypertension, Resistant to Conventional Therapy
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
CROSSOVER
Primary Study Purpose
TREATMENT
Blinding Strategy
TRIPLE
Participants
Caregivers
Investigators
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Spironolactone
Each patient will patients will receive in random order 12 weeks treatment with each of the three active drugs (spironolactone, bisoprolol, doxazosin) or placebo. The dose will be doubled at the six week visit half-way through each phase.
Group Type
ACTIVE_COMPARATOR
Spironolactone
Intervention Type
DRUG
Spironolactone 25mg tablet orally once daily for 6 weeks, followed by Spironolactone 50mg tablet orally once daily for a further 6 weeks.
Placebo
Each patient will patients will receive in random order 12 weeks treatment with each of the three active drugs (spironolactone, bisoprolol, doxazosin) or placebo. The dose will be doubled at the six week visit half-way through each phase
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
Placebo treatment for 12 weeks.
Doxazosin
Each patient will patients will receive in random order 12 weeks treatment with each of the three active drugs (spironolactone, bisoprolol, doxazosin) or placebo. The dose will be doubled at the six week visit half-way through each phase
Group Type
ACTIVE_COMPARATOR
Doxazosin
Intervention Type
DRUG
Doxazosin 4mg tablet orally once daily for 6 weeks, followed by Doxazosin 8mg tablet orally once daily for a further 6 weeks.
Bisoprolol
Each patient will patients will receive in random order 12 weeks treatment with each of the three active drugs (spironolactone, bisoprolol, doxazosin) or placebo. The dose will be doubled at the six week visit half-way through each phase
Group Type
ACTIVE_COMPARATOR
Bisoprolol
Intervention Type
DRUG
Bisoprolol 5mg tablet orally once each day for 6 weeks, followed by Bisoprolol 10mg tablet orally once each day for a further 6 weeks.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Spironolactone
Spironolactone 25mg tablet orally once daily for 6 weeks, followed by Spironolactone 50mg tablet orally once daily for a further 6 weeks.
Intervention Type
DRUG
Bisoprolol
Bisoprolol 5mg tablet orally once each day for 6 weeks, followed by Bisoprolol 10mg tablet orally once each day for a further 6 weeks.
Intervention Type
DRUG
Doxazosin
Doxazosin 4mg tablet orally once daily for 6 weeks, followed by Doxazosin 8mg tablet orally once daily for a further 6 weeks.
Intervention Type
DRUG
Placebo
Placebo treatment for 12 weeks.
Intervention Type
DRUG
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* M/F 18-79 years
* Patients with hypertension not controlled to target: clinic systolic BP ≥ 5 mmHg above target (i.e. ≥ 140 mmHg for non-diabetic hypertensives or ≥ 135 mmHg for diabetics), under one of the following conditions:
1. Treatment for at least 3 months with lisinopril 20 mg (A) + amlodipine 10 mg (C) + bendroflumethiazide 2.5 mg (D) or their equivalents
2. Patients who have received the three drugs or equivalents specified in a), and are either intolerant to one category, or tolerate only a lower dose (e.g. amlodipine 5 mg or lisinopril 10 mg)
3. Patients receiving the three drugs or equivalents specified in a), who are receiving additional drugs for their hypertension, may be included if the investigator: 1) feels it is appropriate to stop these additional drugs at the screening visit and 2) anticipates that the BP criteria for inclusion will be met when re-checked at the baseline visit Patients may be included if the PI anticipates BP criteria for inclusion will be met at randomisation.
* Patients with a home systolic BP average of \>130 mmHg or within 15mmHg of clinic BP over the 4 days prior to the baseline visit.
Exclusion;
* Inability to give informed consent;
* Participation in a clinical study involving an investigational drug or device within 4 weeks of screening;
* Secondary or accelerated hypertension;
* Type 1 diabetes;
* eGFR\<45 mls/min;
* Plasma potassium outside of normal range on two successive measurements during screening;
* Pregnancy, planning to conceive, or women of child-bearing potential not taking adequate contraception
* Anticipated change of medical status during the trial - Absolute contra-indication to study drugs or previous intolerance of trial therapy;
* Sustained atrial fibrillation;
* Recent cardiovascular event requiring hospitalisation
* Suspected non-adherence to antihypertensive treatment
* Requirement for study drug for reason other than to treat hypertension, - Current therapy for cancer;
* Concurrent chronic illness, likely to preclude 52 week participation in the study;
* Clinic Systolic BP \>200 mmHg or diastolic BP \>120mmHg, with PI discretion to override if home BP measurements are lower
* Any concomitant condition that may adversely affect the safety/ efficacy of study drug or severely limit that patients life-span or ability to complete the study
* Treatment with any of the following medications;
1. Oral corticosteroids within 3 months of screening. Treatment with systemic corticosteroids is also prohibited during study participation;
2. Chronic stable use, or unstable use of NSAIDs (other than low dose aspirin) is prohibited. Chronic use defined as \>3 consecutive or non-consecutive days of treatment per week. In addition intermittent use of NSAIDs is strongly discouraged; if required, must not be used for more than a total of 2 days. For those requiring analgesics; paracetamol is recommended.
3. The use of short acting nitrates is permitted, but must not be taken within 4 hours of screening or subsequent visits
4. The use of long acting nitrates is permitted but dose must be stable for at least 2 weeks prior to screening and randomisation;
5. The use of sympathomimetic decongestants is permitted;but not within 1 day prior to any study visit/BP assessment;
6. The use of theophylline is permitted but dose must be stable for 4 weeks prior to screening and throughout the study;
7. The use of phosphodiesterase type V inhibitors is permitted; however study participants must refrain from taking these medications for at least 1 day prior to screening or any subsequent study visits;
8. The use of alpha-blockers is not permitted, with the exception of afluzosin and tamsulosin for prostatic symptoms
* A pill count will be made at the end of the 4 week run-in period and those with adherence \<70% will be excluded from randomisation
* Patients with hypertension not controlled to target: clinic systolic BP ≥ 5 mmHg above target (i.e. ≥ 140 mmHg for non-diabetic hypertensives or ≥ 135 mmHg for diabetics), under one of the following conditions:
1. Treatment for at least 3 months with lisinopril 20 mg (A) + amlodipine 10 mg (C) + bendroflumethiazide 2.5 mg (D) or their equivalents
2. Patients who have received the three drugs or equivalents specified in a), and are either intolerant to one category, or tolerate only a lower dose (e.g. amlodipine 5 mg or lisinopril 10 mg)
3. Patients receiving the three drugs or equivalents specified in a), who are receiving additional drugs for their hypertension, may be included if the investigator: 1) feels it is appropriate to stop these additional drugs at the screening visit and 2) anticipates that the BP criteria for inclusion will be met when re-checked at the baseline visit Patients may be included if the PI anticipates BP criteria for inclusion will be met at randomisation.
* Patients with a home systolic BP average of \>130 mmHg or within 15mmHg of clinic BP over the 4 days prior to the baseline visit.
Exclusion;
* Inability to give informed consent;
* Participation in a clinical study involving an investigational drug or device within 4 weeks of screening;
* Secondary or accelerated hypertension;
* Type 1 diabetes;
* eGFR\<45 mls/min;
* Plasma potassium outside of normal range on two successive measurements during screening;
* Pregnancy, planning to conceive, or women of child-bearing potential not taking adequate contraception
* Anticipated change of medical status during the trial - Absolute contra-indication to study drugs or previous intolerance of trial therapy;
* Sustained atrial fibrillation;
* Recent cardiovascular event requiring hospitalisation
* Suspected non-adherence to antihypertensive treatment
* Requirement for study drug for reason other than to treat hypertension, - Current therapy for cancer;
* Concurrent chronic illness, likely to preclude 52 week participation in the study;
* Clinic Systolic BP \>200 mmHg or diastolic BP \>120mmHg, with PI discretion to override if home BP measurements are lower
* Any concomitant condition that may adversely affect the safety/ efficacy of study drug or severely limit that patients life-span or ability to complete the study
* Treatment with any of the following medications;
1. Oral corticosteroids within 3 months of screening. Treatment with systemic corticosteroids is also prohibited during study participation;
2. Chronic stable use, or unstable use of NSAIDs (other than low dose aspirin) is prohibited. Chronic use defined as \>3 consecutive or non-consecutive days of treatment per week. In addition intermittent use of NSAIDs is strongly discouraged; if required, must not be used for more than a total of 2 days. For those requiring analgesics; paracetamol is recommended.
3. The use of short acting nitrates is permitted, but must not be taken within 4 hours of screening or subsequent visits
4. The use of long acting nitrates is permitted but dose must be stable for at least 2 weeks prior to screening and randomisation;
5. The use of sympathomimetic decongestants is permitted;but not within 1 day prior to any study visit/BP assessment;
6. The use of theophylline is permitted but dose must be stable for 4 weeks prior to screening and throughout the study;
7. The use of phosphodiesterase type V inhibitors is permitted; however study participants must refrain from taking these medications for at least 1 day prior to screening or any subsequent study visits;
8. The use of alpha-blockers is not permitted, with the exception of afluzosin and tamsulosin for prostatic symptoms
* A pill count will be made at the end of the 4 week run-in period and those with adherence \<70% will be excluded from randomisation
Minimum Eligible Age
18 Years
Maximum Eligible Age
79 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
British Heart Foundation
OTHER
Sponsor Role
collaborator
University of Cambridge
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Morris Brown
Professor
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Prof MJ Brown
Role: PRINCIPAL_INVESTIGATOR
University of Cambridge
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
NHS Ayrshire
Ayrshire, , United Kingdom
Site Status
University Hospitals Birmingham NHS Foundation Trust
Birmingham, , United Kingdom
Site Status
University of Birmingham
Birmingham, , United Kingdom
Site Status
University of Cambridge - Addenbrookes Hospital
Cambridge, , United Kingdom
Site Status
NHS Tayside/University of Dundee
Dundee, , United Kingdom
Site Status
NHS Lothian/University of Edinburgh
Edinburgh, , United Kingdom
Site Status
Royal Devon & Exeter NHS Foundation Trust
Exeter, , United Kingdom
Site Status
NHS Greater Glasgow and Clyde/University of Glasgow
Glasgow, , United Kingdom
Site Status
Ixworth GP Practice
Ixworth, , United Kingdom
Site Status
University Hospitals of Leicester NHS Trust
Leicester, , United Kingdom
Site Status
Barts and the London School of Medicine and Dentistry
London, , United Kingdom
Site Status
Guys and St Thomas' NHS Foundation Trust
London, , United Kingdom
Site Status
Imperial College Healthcare NHS Trust
London, , United Kingdom
Site Status
Central Manchester University Hospitals NHS Foundation Trust
Manchester, , United Kingdom
Site Status
Norfolk and Norwich University Hospital NHS Trust
Norwich, , United Kingdom
Site Status
West Hertfordshire Hospitals NHS Trust
Watford, , United Kingdom
Site Status
Countries
Review the countries where the study has at least one active or historical site.
United Kingdom
References
Explore related publications, articles, or registry entries linked to this study.
NICE/BHS. CG34 Hypertension - NICE guideline (all the recommendations). http://www.nice.org.uk/guidance/CG34/niceguidance /pdf/english 2006
Reference Type
BACKGROUND
Dickerson JE, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet. 1999 Jun 12;353(9169):2008-13. doi: 10.1016/s0140-6736(98)07614-4.
Reference Type
BACKGROUND
Deary AJ, Schumann AL, Murfet H, Haydock SF, Foo RS, Brown MJ. Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs. J Hypertens. 2002 Apr;20(4):771-7. doi: 10.1097/00004872-200204000-00037.
Reference Type
BACKGROUND
Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension. 2002 May;39(5):982-8. doi: 10.1161/01.hyp.0000016176.16042.2f.
Reference Type
BACKGROUND
Kaplan NM. Resistant hypertension. J Hypertens. 2005 Aug;23(8):1441-4. doi: 10.1097/01.hjh.0000174968.72212.ac.
Reference Type
BACKGROUND
Black HR, Keck M, Meredith P, Bullen K, Quinn S, Koren A. Controlled-release doxazosin as combination therapy in hypertension: the GATES study. J Clin Hypertens (Greenwich). 2006 Mar;8(3):159-66; quiz 167-8. doi: 10.1111/j.1524-6175.2006.04811.x.
Reference Type
BACKGROUND
Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003 Jun 28;326(7404):1427. doi: 10.1136/bmj.326.7404.1427.
Reference Type
BACKGROUND
Brown MJ, Cruickshank JK, Dominiczak AF, MacGregor GA, Poulter NR, Russell GI, Thom S, Williams B; Executive Committee, British Hypertension Society. Better blood pressure control: how to combine drugs. J Hum Hypertens. 2003 Feb;17(2):81-6. doi: 10.1038/sj.jhh.1001511.
Reference Type
BACKGROUND
Williams B, MacDonald TM, Morant SV, Webb DJ, Sever P, McInnes GT, Ford I, Cruickshank JK, Caulfield MJ, Padmanabhan S, Mackenzie IS, Salsbury J, Brown MJ; British Hypertension Society programme of Prevention And Treatment of Hypertension With Algorithm based Therapy (PATHWAY) Study Group. Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies. Lancet Diabetes Endocrinol. 2018 Jun;6(6):464-475. doi: 10.1016/S2213-8587(18)30071-8. Epub 2018 Apr 11.
Reference Type
DERIVED
Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, Ford I, Cruickshank JK, Caulfield MJ, Salsbury J, Mackenzie I, Padmanabhan S, Brown MJ; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015 Nov 21;386(10008):2059-2068. doi: 10.1016/S0140-6736(15)00257-3. Epub 2015 Sep 20.
Reference Type
DERIVED
Williams B, MacDonald TM, Caulfield M, Cruickshank JK, McInnes G, Sever P, Webb DJ, Salsbury J, Morant S, Ford I, Brown MJ. Prevention And Treatment of Hypertension With Algorithm-based therapy (PATHWAY) number 2: protocol for a randomised crossover trial to determine optimal treatment for drug-resistant hypertension. BMJ Open. 2015 Aug 7;5(8):e008951. doi: 10.1136/bmjopen-2015-008951.
Reference Type
DERIVED
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2008-007149-30
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
UKCRN 4500
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Treatment of High Blood Pressure Using Olmesartan With Hydrochlorothiazide Compared to an ACE Inhibitor With a Calcium Channel Blocker
NCT00185120
COMPLETED
PHASE4
Efficacy and Safety of Valsartan Versus Amlodipine in Postmenopausal Women With Hypertension
NCT00171054
COMPLETED
PHASE4
Combination of Benazepril Plus Hydrochlorothiazide in Chinese Patients With Mild to Moderate Essential Hypertension
NCT00367094
COMPLETED
PHASE3
Efficacy and Tolerability of an Aliskiren-based Treatment Algorithm in Patients With Mild to Moderate Hypertension
NCT00765947
COMPLETED
PHASE4
A Clinical Study to Compare Long-term Efficacy and Safety of an Aliskiren Based Regimen to a Hydrochlorothiazide Based Treatment Regimen With Optional Addition of Amlodipine
NCT00294710
COMPLETED
PHASE3
Efficacy and Safety of Valsartan/Hydrochlorothiazide Combination Compared to Valsartan Monotherapy or Hydrochlorothiazide Monotherapy in Elderly (>70) With Mild-moderate Hypertension.
NCT00698646
COMPLETED
PHASE4
A Clinical Study to Compare an Aliskiren Based Hypertensive Regimen With a Ramipril Based One Followed by a Randomized Withdrawal.
NCT00219063
COMPLETED
PHASE3
Study of the Efficacy and Safety of the Combination of Two FDA Approved Oral Medications, Nebivolol and Valsartan for Treatment of Stage 1 or 2 Hypertension
NCT01508026
COMPLETED
PHASE3
Clinical One-stage Controlled Study of reSistant Arterial Hypertension for the desiGning of a personAlized Approach to Therapy
NCT05899920
RECRUITING
NA
A Clinical Study to Evaluate the Effects of Darusentan on Safety and Efficacy in Subjects With Resistant Systolic Hypertension Receiving Combination Therapy With Three or More Blood Pressure Lowering Drugs
NCT00364026
COMPLETED
PHASE2
A Clinical Study to Compare the Safety and Efficacy of an Aliskiren-based Regimen With a Lisinopril Based Regimen in Patients With Severe Hypertension
NCT00219050
COMPLETED
PHASE3
Efficacy and Safety of Aliskiren 75 mg, 150 mg, and 300 mg in Elderly Patients With Essential Hypertension When Given With a Light Meal in a 8 Week Placebo-controlled Study
NCT00706134
COMPLETED
PHASE3
Aliskiren and the Calcium Channel Blocker Amlodipine Combination as an Initial Treatment Strategy for Hypertension
NCT00797862
COMPLETED
PHASE3
Effectiveness of a Valsartan Based vs an Amlodipine Based Treatment Strategy in naïve Patients With Stage 1 or Stage 2 Hypertension or in Patients Uncontrolled on Current Monotherapy
NCT00351130
COMPLETED
PHASE4
Blood Pressure Lowering of Aliskiren Hydrochlorothiazide (HCTZ) Versus Amlodipine in Stage 2 Hypertension in African Americans
NCT00739596
COMPLETED
PHASE4
Efficacy and Safety of Valsartan/Hydrochlorothiazide Combination Therapy in Patients With Hypertension
NCT00280540
COMPLETED
PHASE4
Efficacy and Safety of Valsartan Plus Hydrochlorothiazide in Fixed Dose Combination in Hypertensive Patients Not Controlled by the Free Combination of an Angiotensin Receptor Blocker Plus Hydrochlorothiazide
NCT00360178
COMPLETED
PHASE3
Efficacy and Safety of Valsartan and Amlodipine (± HCTZ) in Adults With Moderate, Inadequately Controlled Hypertension
NCT00523744
COMPLETED
PHASE3
Study of CS-3150 in Patients With Severe Hypertension
NCT02808026
COMPLETED
PHASE3
SPP100 (Aliskiren) Regimen in Patients With Severe Hypertension
NCT00299806
COMPLETED
PHASE3
Efficacy and Safety of SPA100 (Fixed-dose Combination of Aliskiren/Amlodipine) in Patients With Essential Hypertension
NCT01237223
COMPLETED
PHASE3
Valsartan/Hydrochlorothiazide Combination vs Amlodipine in Patients With Hypertension, Diabetes, and Albuminuria.
NCT00171561
COMPLETED
PHASE4
A Clinical Study to Assess Efficacy and Safety of Aliskiren in the Elderly With High Blood Pressure
NCT00219167
COMPLETED
PHASE3