Resistant HypertensionPhase 4NCT04331691
Comparison of Spironolactone and Amiloride on Home Blood Pressure in Resistant Hypertension
A Phase 4 study testing Spironolactone and Amiloride in people with Resistant Hypertension, run by Yonsei University at 1 site in South Korea.
Trial summary
Resistant hypertension is defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes including diuretics. Patients with resistant hypertension has at least 1.5-fold higher cardiovascular risk than those with non-resistant hypertension. Read more about this study
- Who is it for?
- Ages 19 to 75 years
- Conditions the study is for
- Resistant Hypertension
- What is being tested?
- Spironolactone and Amiloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteSouth Korea
- Study dates
- 16 Nov 2020to 23 May 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 19-75
- Patients with resistant hypertension
- 1st screening: ven while taking three or more types of antihypertensive medications including diuretics without changing the dose for 1 month, the average office systolic blood pressure measured in three times is 130-180 mmHg and daytime systolic blood pressure is ≥130 mmHg.
- 2nd screening: An average systolic blood pressure of home blood pressure monitoring is ≥130 mmHg during the run-in period of antihypertensive drugs including diuretics (Sevikar HCT 5/20/12.5 mg, 5/40/12.5 mg or 10/40/12.5 mg).
- Patients with resistant hypertension who have agreed to participate in the study: when they have the ability to write a written consent in accordance with the Korean Good Clinical Practice (KGCP) and local laws.
- Patients who can change the currently used antihypertensive treatment to Sevikar HCT 5/20/12.5 mg, 5/40/12.5 mg or 10/40/12.5 mg without giving unacceptable risk (investigator's judgment)
Who cannot join
- White-coat uncontrolled hypertension
- Severe hypertension (WHO classification criteria grade 3 average diastolic blood pressure ≥ 110 mmHg or average systolic blood pressure ≥ 180 mmHg)
- Known cardiovascular disease (including stroke and TIA), including a history of angina, heart failure, myocardial infarction or revascularization, or cerebrovascular disease prior to 6 months
- Congestive heart failure of III-IV according to NYHA functional classification
- Clinically meaningful ventricular tachycardia, atrial fibrillation, atrial flutter, or other arrhythmia that the investigator has deemed clinically meaningful.
- Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve or stenosis on the mitral valve
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- Renal insufficiency (basal estimated glomerular filtration rate (eGFR) <50 ml / min / 1.73m2)
- Hyperkalemia (> 5.0 mmol / L, which can be reconfirmed if errors are suspected in the results)
- Gastrointestinal diseases that can cause potential malabsorption the gastro-intestinal tract is severely narrowed; Kock pouch (a continent pouch formed by the terminal ileum after colectomy)
- Bile stasis or biliary obstruction
- liver disease or aspartate aminotransferase (AST) / alanine aminotransferase (ALT) levels > 2-fold the normal upper limit (ULN)
- Pregnant or fertile women who are not contraceptive or woman who are lactating
- Intolerant to test drug/drug group or its components
- Subjects who are currently participating in other clinical trials and who have taken other investigational product within the past month.
- Subjects who have condition or a disease that may impede the completion of the test, according to the investigator's opinion
- If assigned to treatment for this trial in the past
- Uncorrected sodium or fluid depletion
- History of drug or alcohol dependence within 6 months
- The combination of medications known to affect blood pressure, except those permitted by the protocol.
- Other clinical conditions that, as determined by the investigator, cannot be safely completed according to the protocol or that the investigational product cannot be safely used a history of secondary hypertension that cannot be corrected
- Taking spironolactone or amiloride within 4 weeks from the time of screening
- If discontinued due to side effects of spironolactone or amiloride
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Severance Cardiovascular Hospital, Yonsei University Health System
Seoul
About this study
Official title: SPironolactone Versus Amiloride for Treatment of REsistant Hypertension (SPARE Trial): A Comparison of Home Blood Pressure
Resistant hypertension is defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes including diuretics. Patients with resistant hypertension has at least 1.5-fold higher cardiovascular risk than those with non-resistant hypertension. Therefore, controlling blood pressure is crucial in patients with resistant hypertension.
It has been unclear which antihypertensive agent should be added in patients who cannot reach target blood pressure despite use of three antihypertensive agents. There have been three randomized clinical trials that proved the efficacy of spironolactone in resistant hypertension, but they were small sized, comparison study to placebo. Recently published PATHWAY-2 study which compared the efficacy of spironolactone with placebo, doxazosin, and bisoprolol showed superiority of spironolactone in blood pressure lowering in patients with resistant hypertension. Thus, revised ACC/AHA and ESC/ESH guideline for arterial hypertension recommended spironolactone as the fourth agent for resistant hypertension. However, in real world, adherence to spironolactone may not be adequate because of adverse effect such as gynecomastia, hyperkalemia, and so on.
Read more
Recently, sub-study of PATHWAY-2 revealed that amiloride changes systolic blood pressure by -22.2 mmHg (95% CI, -24.7 to -19.7) which is comparable with the effect of spironolactone (-21.8 mmHg; 95% CI, -24.2 to -19.3). However, it was not randomized clinical trial to compare the effect between spironolactone and amiloride in patients with resistant hypertension.
This study aims to compare the effect of spironolactone and amiloride on home blood pressure in resistant hypertensive patients and to compare the rate of target blood pressure achievement between spironolactone and amiloride in resistant hypertensive patients.
Read the detailed description
The subjects with office SBP of 130-180 mmHg with 3 antihypertensive medications of different classes including thiazide or thiazide-like diuretics and daytime average daytime SBP of ≥ 130 mmHg are enrolled in the 4-week run-in period. During run-in period, subjects will receive sevikar HCT (5/20/12.5 mg, 5/40/12.5 mg or 10/40/12.5 mg). After a 4-week run-in period, subjects who have uncontrolled average home SBP, defined as average SBP of ≥ 130 mmHg, will be randomized to either spironolactone or amiloride. 118 subjects will be randomly assigned to one of the two treatment groups. Subjects randomly assigned to one of the two treatment groups will receive 12.5 mg of spironolactone and the other group will receive 5 mg of amiloride. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 25 mg of spironolactone or 10 mg of amiloride. After 12 weeks of treatment, study will be end.
- Conditions
- Resistant Hypertension
- Being tested
- Spironolactone, Amiloride
- Keywords
- Resistant Hypertension, Spironolactone, Amiloride, Home Blood Pressure Monitoring
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
After randomization, this group will receive 12.5 mg of spironolactone daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 25 mg of spironolactone. After 12 weeks of treatment, study will be end.
AmilorideDrug
After randomization, this group will receive 5 mg of amiloride daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 10 mg of amiloride. After 12 weeks of treatment, study will be end.
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Active comparator | After randomization, this group will receive 12.5 mg of spironolactone daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 25 mg of spironolactone. After 12 weeks of treatment, study will be end. Receives: Drug: Spironolactone |
| Amiloride | Experimental | After randomization, this group will receive 5 mg of amiloride daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 10 mg of amiloride. After 12 weeks of treatment, study will be end. Receives: Drug: Amiloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference between spironolactone versus amiloride for changes in home SBP from baseline to week 12.
Comparison of the change of average home systolic blood pressure at week 12 from the introduction phase between spironolactone group and amiloride group
Measured: week 12
Secondary outcomes (1)
target blood pressure achievement rates
Comparison of achievement rate for target home and office BP between spironolactone group and amiloride group
Measured: week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2020
- Study start16 Nov 2020
- Primary completion23 May 2024
- Study completion23 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Resistant HypertensionStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sungha Park, Principal investigator, Severance Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04331691
- Sponsor's protocol ID
- 4-2019-1334
- Status last verified
- Sep 2024
- First submitted
- 31 Mar 2020
- Last updated
- 24 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lee CJ, Ihm SH, Shin DH, Jeong JO, Kim JH, Chun KH, Ryu J, Lee HY, Choi S, Lee EM, Choi JH, Kim KI, Shin J, Pyun WB, Kim DH, Park S, Williams B. Spironolactone vs Amiloride for Resistant Hypertension: A Randomized Clinical Trial. JAMA. 2025 Jun 17;333(23):2073-2082. doi: 10.1001/jama.2025.5129.
PubMed 40366680
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SPironolactone Versus Amiloride for Treatment of REsistant Hypertension (SPARE Trial): A Comparison of Home Blood Pressure
- ClinicalTrials.gov ID
- NCT04331691
- Acronym / sponsor ID
- 4-2019-1334
- Conditions
- Resistant Hypertension
- Keywords
- Resistant Hypertension, Spironolactone, Amiloride, Home Blood Pressure Monitoring
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 16 Nov 2020 (actual)
- Primary completion
- 23 May 2024 (actual)
- Study completion
- 23 May 2024 (actual)
- First posted
- 2 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Resistant hypertension is defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes including diuretics. Patients with resistant hypertension has at least 1.5-fold higher cardiovascular risk than those with non-resistant hypertension. Therefore, controlling blood pressure is crucial in patients with resistant hypertension.
It has been unclear which antihypertensive agent should be added in patients who cannot reach target blood pressure despite use of three antihypertensive agents. There have been three randomized clinical trials that proved the efficacy of spironolactone in resistant hypertension, but they were small sized, comparison study to placebo. Recently published PATHWAY-2 study which compared the efficacy of spironolactone with placebo, doxazosin, and bisoprolol showed superiority of spironolactone in blood pressure lowering in patients with resistant hypertension. Thus, revised ACC/AHA and ESC/ESH guideline for arterial hypertension recommended spironolactone as the fourth agent for resistant hypertension. However, in real world, adherence to spironolactone may not be adequate because of adverse effect such as gynecomastia, hyperkalemia, and so on.
Recently, sub-study of PATHWAY-2 revealed that amiloride changes systolic blood pressure by -22.2 mmHg (95% CI, -24.7 to -19.7) which is comparable with the effect of spironolactone (-21.8 mmHg; 95% CI, -24.2 to -19.3). However, it was not randomized clinical trial to compare the effect between spironolactone and amiloride in patients with resistant hypertension.
This study aims to compare the effect of spironolactone and amiloride on home blood pressure in resistant hypertensive patients and to compare the rate of target blood pressure achievement between spironolactone and amiloride in resistant hypertensive patients.
Detailed description
The subjects with office SBP of 130-180 mmHg with 3 antihypertensive medications of different classes including thiazide or thiazide-like diuretics and daytime average daytime SBP of ≥ 130 mmHg are enrolled in the 4-week run-in period. During run-in period, subjects will receive sevikar HCT (5/20/12.5 mg, 5/40/12.5 mg or 10/40/12.5 mg). After a 4-week run-in period, subjects who have uncontrolled average home SBP, defined as average SBP of ≥ 130 mmHg, will be randomized to either spironolactone or amiloride. 118 subjects will be randomly assigned to one of the two treatment groups. Subjects randomly assigned to one of the two treatment groups will receive 12.5 mg of spironolactone and the other group will receive 5 mg of amiloride. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 25 mg of spironolactone or 10 mg of amiloride. After 12 weeks of treatment, study will be end.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Active comparator | Drug: SpironolactoneAfter randomization, this group will receive 12.5 mg of spironolactone daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 25 mg of spironolactone. After 12 weeks of treatment, study will be end. |
| Amiloride | Experimental | Drug: AmilorideAfter randomization, this group will receive 5 mg of amiloride daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 10 mg of amiloride. After 12 weeks of treatment, study will be end. |
Who may qualify
- Ages
- 19 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 19-75
- Patients with resistant hypertension
- Patients with resistant hypertension who have agreed to participate in the study: when they have the ability to write a written consent in accordance with the Korean Good Clinical Practice (KGCP) and local laws.
- Patients who can change the currently used antihypertensive treatment to Sevikar HCT 5/20/12.5 mg, 5/40/12.5 mg or 10/40/12.5 mg without giving unacceptable risk (investigator's judgment)
Key exclusion criteria (22 listed)
- White-coat uncontrolled hypertension
- Severe hypertension (WHO classification criteria grade 3 average diastolic blood pressure ≥ 110 mmHg or average systolic blood pressure ≥ 180 mmHg)
- Known cardiovascular disease (including stroke and TIA), including a history of angina, heart failure, myocardial infarction or revascularization, or cerebrovascular disease prior to 6 months
- Congestive heart failure of III-IV according to NYHA functional classification
- Clinically meaningful ventricular tachycardia, atrial fibrillation, atrial flutter, or other arrhythmia that the investigator has deemed clinically meaningful.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SpironolactoneAfter randomization, this group will receive 12.5 mg of spironolactone daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 25 mg of spironolactone. After 12 weeks of treatment, study will be end. | Drug | Spironolactone |
| AmilorideAfter randomization, this group will receive 5 mg of amiloride daily. Subjects who did not reach the target blood pressure after 4 weeks of treatment should be increased to 10 mg of amiloride. After 12 weeks of treatment, study will be end. | Drug | Amiloride |
Primary outcome
The difference between spironolactone versus amiloride for changes in home SBP from baseline to week 12.
Time frame: week 12
Comparison of the change of average home systolic blood pressure at week 12 from the introduction phase between spironolactone group and amiloride group
1 secondary outcome
target blood pressure achievement rates
Time frame: week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
- Derived from this study: PubMed 40366680Lee CJ, Ihm SH, Shin DH, Jeong JO, Kim JH, Chun KH, Ryu J, Lee HY, Choi S, Lee EM, Choi JH, Kim KI, Shin J, Pyun WB, Kim DH, Park S, Williams B. Spironolactone vs Amiloride for Resistant Hypertension: A Randomized Clinical Trial. JAMA. 2025 Jun 17;333(23):2073-2082. doi: 10.1001/jama.2025.5129.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sungha Park principal investigator
Severance Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Spironolactone and Amiloride in people with Resistant Hypertension, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference between spironolactone versus amiloride for changes in home SBP from baseline to week 12. (time frame: week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04331691, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.