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HypertensionPhase 4ESPECIALNCT01552954

Effects of Low Sodium Intake on the Anti-proteinuric Efficacy in Hypertensive Patient With Olmesartan

A Phase 4 study testing Intensive education of low salt diet in people with Hypertension and Chronic Kidney Disease, run by Seoul National University Bundang Hospital at 7 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Purpose of this study 1. Intensive education for low salt diet will be enhance the anti-proteinuric effect of Olmesartan, a popular anti-hypertensive drug of angiotensin II receptor blocker, in Koreans compared to conventional prescription of medication. 2. Read more about this study

Who is it for?
Ages 19 to 75 years
What is being tested?
Intensive education of low salt diet
Could I receive a placebo?
No, everyone receives an active treatment
How many people
269 participants
Where
7 sitesSouth Korea
Study dates
Feb 2012to Oct 2013
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Aged 19 years or more and 75 years or less
  • Hypertension patients: Patients whose blood pressure is 140/90mmHg and over, patients is newly diagnosed with hypertension or is prescribed antihypertensive medications.
  • Hypertensive patients verified 2 times or more of albuminuria 30 mg/g cr or more in a spot urine sample with interval of 1 week or more in recent 6 months
  • Estimated glomerular filtration rate (GFR) by Modification of Diet in Renal Disease (MDRD) equation 30 ml/min/1.73 m2 or more
  • Patients who give written consent to this study by oneself

Who cannot join

  • Blood pressure more than 160/100 mmHg
  • Pregnant
  • Serum potassium level more than 5.5 mEq/L at screening period
  • Patients with malignancy, acute cerebral infarction, acute myocardial infarction, unstable angina, percutaneous coronary arterial intervention (PCI), or coronary artery bypass graft (CABG) in recent 6 months
  • Patients with diabetes mellitus
  • Patients who have an allergy to Olmesartan
  • Patients who were involved in other clinical trial in recent 1 month or are participated in screening period
  • Patients taking medication(s) of corticosteroid or immunosuppressant in a screening period

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

South Korea7 sites

  • Dongguk University Ilsan Hospital

    Ilsan, Kyeongki, 410773

  • Seoul National University Bundang Hospital

    Seongnam, Kyeong Ki, 463787

  • Seoul National University Hospital

    Seoul, Seoul, 110744

  • Kyung Hee University

    Seoul, Seoul, 134727

  • Seoul St. Mary's Hospital

    Seoul, Seoul, 137701

  • Konkuk University School of Medicine

    Seoul, Seoul, 143729

  • SMG-SNU Boramae Medical Center

    Seoul, Seoul, 156707

Other trials in South Korea

About this study

Official title: Effects of Low Sodium Intake on the Anti-proteinuric Efficacy of Olmesartan in Hypertensive Patients With Albuminuria Through Open-label Randomized Trial

Purpose of this study

  1. Intensive education for low salt diet will be enhance the anti-proteinuric effect of Olmesartan, a popular anti-hypertensive drug of angiotensin II receptor blocker, in Koreans compared to conventional prescription of medication.
  2. Intensive education for low salt diet will decrease the amount of 24 hour-urine sodium excretion compared to control group, effectively.
Read the detailed description
  1. Background
  2. The chronic kidney disease (CKD) is the one of the main burden of chronic diseases and the prevalence of CKD is increasing in worldwide. In Korea, the prevalence of CKD was reported as 13.7% among urban Korean adults in 2008 by our study group.
  3. It is well known the CKD is the most important risk factor to cardiovascular events, cardiovascular mortality, all cause-mortality, and hospitalization. The cost of the management for the CKD was high and it took 3.25% of all budgets for medical reimbursement in 2004 for all Koreans, which was ranked on the top of expenditure for single disease category.
  4. The most popular risk factors to CKD progression are aging, obesity, hyperlipidemia, diabetes mellitus, hypertension, and proteinuria. The hypertension and proteinuria also cause the cardiovascular events and increase the mortality rate.
  5. The inhibitors for renin-angiotensin aldosterone system, angiotensin II type I receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI), are well known medications to prevent cardiovascular events and renal functional deterioration to end stage renal disease(ESRD) in patients with hypertension, non-diabetic CKD, or diabetic nephropathy. One of the adverse events of ARB is the decrease of hemoglobin. Inoue et al reported the level of hemoglobin was decreased in amount of 0.45 ±0.89 g/dL after prescription of ARB and valsartan decreased the erythropoietin in 6 days after medication. The exact mechanism of decrease of hemoglobin by ARB was not fully verified but it is related to decrease effects of angiotensin II on aggravating hypoxia in the kidney and on the activation of hypoxia-inducible factor 1α (HIF1a) and then decrease the production of erythropoietin as in the report of Durmus et al. Considering that the relationships between ARB usage and decrease of proteinuria in transplanted kidney, between aggravation of hypoxia or HIF1a and CKD, and between ARB and the decrease of HIF1a or erythropoietin(EPO), we could postulate that the decrease of hemoglobin would not be a adverse effect of ARB to deteriorate patients' condition but a co-phenomenon of ARB's anti-RAS effect and a marker of ARB's effectiveness.
  6. The anti-proteinuric effect of ARB is decreased by high salt intake. For example, ARB treatment without low salt intake decreased proteinuria by 30% in patients with proteinuria 2-10g/day compared to baseline value and addition of low salt diet to ARB treatment further decreased proteinuria up to 25%. But, using slow salt tablets, increase of daily intake of sodium diminished the anti-proteinuric effect of ARB in diabetic nephropathy.
  7. The previous studies for the effect of ARB on proteinuria affected by sodium intake took the methods of controlled diet by researcher or using slow salt tablet but these method are not practical to adopt in real clinical practice.
  8. The moderate and mild decrease of daily sodium intake which lower the daily excretion of sodium by 55 mEq/day had an effect of decrease of proteinuria by 11% in hypertensive patients.
  9. The mean amount of sodium of Korean diets was reported as high as 208 mmol/day in Intersalt study, which is more than 11 g of salt. The recent reports also showed the trend of high salt-intake by Koreans.
  10. Rationale So, It is worth to do this study because
  • high salt intake is prevalent in Koreans,
  • high salt diet diminishes the effect of ARB on proteinuria
  • the methods used in previous studies were not suitable to apply to clinical practice,
  • and there were no study to reveal the decrease of hemoglobin would the marker for the effect of ARB and not be a adverse event of ARB.
  1. Objectives
  2. Primary objective: The difference between amount of albuminuria after usage of Olmesartan and amount of albuminuria after prescription of Olmesartan with intensive diet education in intervention group is higher than the difference of albuminuria in control group.
  3. Secondary objective: Item 1: In all patients, Olmesartan decreases the albuminuria. Item 2: In all patients, the change of hemoglobin after prescription of Olmesartan is proportional to the change of albuminuria and serum erythropoietin. Item 3: Intensive education for low salt diet induces the significant decrease of daily sodium excretion in Intervention group compared to control group. Item 4: Intensive education for low salt diet induces the significant decrease of blood pressure in Intervention group compared to control group.
  4. Study Flow
  • Period
  1. Washout period (-8 weeks;Point 0 to 0 weeks; Point 1)
  2. Olmesartan Period ( 0 week; point 1 to 8 weeks; point 2)
  3. Intervention period (8 week ; point 2 to 16 weeks; point 3)
  • For patients with taking ACEI, other ARB, diuretics, or renin inhibitor, already; Initial wash-out period for 8 weeks, and then (point 1) prescription of Olmesartan 40 mg qd for 8 weeks, and then (point 2) allocation to Intensive group or control group for 8 weeks, and then the study will be over (point 3).
  • For patients without taking ACEI, other ARB, diuretics, or renin inhibitor; For initial 8 weeks, adjust the blood pressures around 140/90 mmHg, and then (point 1) prescription of Olmesartan 40 mg qd for 8 weeks, and then (point 2) allocation to Intensive group or control group for 8 weeks, and then the study will be over (point 3).
  • Blood pressure control Adjust the blood pressures around 140/90 mmHg with other hypertensive drugs except ACEI, other ARB, diuretics, or renin inhibitor during whole period.
  • Intensive diet education:

For 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks.

Being tested
Intensive education of low salt diet
Keywords
hypertension, Chronic kidney disease, albuminuria, low salt diet, Angiotensin II receptor blocker
Medical subject headings
Hypertension, Renal Insufficiency, Chronic, Albuminuria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intensive education of low salt dietBehavioural

    Also called low salt diet, Angiotensin II converting enzyme, albuminuria, chronic kidney disease

    For 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks.

Study groups in NCT01552954
Study groupRoleWhat they receive
Intensive education of low salt dietExperimentalFor 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks. (*Intervention in this trial is the "intensity of education")
Receives: Behavioral: Intensive education of low salt diet
Conventional diet groupNo interventionEducation for low salt diet will be conducted as in office with brief communication with a patient and a physician.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ∆Albuminuria by 24-hour Urine Protein Excretion

    Change in albuminuria as a 24-hour urine protein excretion by intensive education of low salt diet during taking olmesartan

    *In outcome measure data table, the 24-hour urine collection at 16th week was omitted in 3 out of 245 patients (1 for intensive education group and 2 for conventional education group). Values of each study week were "mean" of all participants on specific study week, but "∆albuminuria (week 8 - week 16)" value was "mean" of ∆ values of "8 weeks-16 weeks" in each individuals. Therefore, values of 3 patients were excluded in "mean of ∆albuminuria (week 8 - week 16)". That's why simple subtraction (week 8 - week 16) of values are not matched with the data.

    Measured: changes from week 8 at week 16 (week 8 - week 16)

Secondary outcomes (3)

  1. ∆Hemoglobin (0 Week - 16 Weeks)

    The change of hemoglobin after prescription of Olmesartan

    Measured: 0 week, 16 weeks

  2. Na Excretion Change in 24 Hour-urine Collection Between Weeks 8 and 16

    Change of sodium excretion rate in 24 hour-urine collection by intensive education for low salt diet at week 16

    Measured: week 8 and week 16

  3. Systolic and Diastolic Blood Pressure Change Between Weeks 8 and 16

    Change in Systolic and Diastolic Blood Pressure from Week 8 to Week 16 in the Intensive Education Group compared to the Conventional Education Group

    Measured: week 8 and week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionJun 2013
  4. Study completionOct 2013

Resources

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
269 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01552954
Sponsor's protocol ID
B-1112/142-008
Acronym
ESPECIAL
Status last verified
Dec 2014
First submitted
24 Feb 2012
Last updated
18 Dec 2014
Data monitoring committee
No

Publications

  • Vogt L, Waanders F, Boomsma F, de Zeeuw D, Navis G. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol. 2008 May;19(5):999-1007. doi: 10.1681/ASN.2007060693. Epub 2008 Feb 13.

    PubMed 18272844

  • Ekinci EI, Thomas G, Thomas D, Johnson C, Macisaac RJ, Houlihan CA, Finch S, Panagiotopoulos S, O'Callaghan C, Jerums G. Effects of salt supplementation on the albuminuric response to telmisartan with or without hydrochlorothiazide therapy in hypertensive patients with type 2 diabetes are modulated by habitual dietary salt intake. Diabetes Care. 2009 Aug;32(8):1398-403. doi: 10.2337/dc08-2297. Epub 2009 Jun 23.

    PubMed 19549737

  • He FJ, Marciniak M, Visagie E, Markandu ND, Anand V, Dalton RN, MacGregor GA. Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives. Hypertension. 2009 Sep;54(3):482-8. doi: 10.1161/HYPERTENSIONAHA.109.133223. Epub 2009 Jul 20.

    PubMed 19620514

  • Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ. 1988 Jul 30;297(6644):319-28. doi: 10.1136/bmj.297.6644.319.

    PubMed 3416162

  • Swift PA, Markandu ND, Sagnella GA, He FJ, MacGregor GA. Modest salt reduction reduces blood pressure and urine protein excretion in black hypertensives: a randomized control trial. Hypertension. 2005 Aug;46(2):308-12. doi: 10.1161/01.HYP.0000172662.12480.7f. Epub 2005 Jun 27.

    PubMed 15983240

  • Hwang JH, Oh S, Chin HJ, Kim S, Kim DK, Kim S, Park JH, Shin SJ, Lee SH, Choi BS, Lim CS. Comparison of the performance of currently used estimated glomerular filtration rate equations with 24-hour urine creatinine clearance: sample analysis of randomised controlled trial participants. BMJ Open. 2023 Aug 23;13(8):e067398. doi: 10.1136/bmjopen-2022-067398.

    PubMed 37612109

  • McMahon EJ, Campbell KL, Bauer JD, Mudge DW, Kelly JT. Altered dietary salt intake for people with chronic kidney disease. Cochrane Database Syst Rev. 2021 Jun 24;6(6):CD010070. doi: 10.1002/14651858.CD010070.pub3.

    PubMed 34164803

  • Conley MM, McFarlane CM, Johnson DW, Kelly JT, Campbell KL, MacLaughlin HL. Interventions for weight loss in people with chronic kidney disease who are overweight or obese. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD013119. doi: 10.1002/14651858.CD013119.pub2.

    PubMed 33782940

  • An JN, Hwang JH, Lee JP, Chin HJ, Kim S, Kim DK, Kim S, Park JH, Shin SJ, Lee SH, Choi BS, Lim CS. The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial. PLoS One. 2015 Jun 22;10(6):e0128632. doi: 10.1371/journal.pone.0128632. eCollection 2015.

    PubMed 26098847

  • Baek SH, Kim S, Kim DK, Park JH, Shin SJ, Lee SH, Choi BS, Chin HJ, Kim S, Lim CS. A low-salt diet increases the estimated net endogenous acid production in nondiabetic chronic kidney disease patients treated with angiotensin receptor blockade. Nephron Clin Pract. 2014;128(3-4):407-13. doi: 10.1159/000369558. Epub 2014 Dec 18.

    PubMed 25531146

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Intensive education of low salt diet in people with Hypertension and Chronic Kidney Disease, run by Seoul National University Bundang Hospital at 7 sites 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 5 inclusion and 8 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 18 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites 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?

Yes. Results are posted in the registry (first posted 18 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

∆Albuminuria by 24-hour Urine Protein Excretion (time frame: changes from week 8 at week 16 (week 8 - week 16)). 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 NCT01552954, which also lists 10 linked publications.

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 18 Dec 2014.

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