Effect of Renin-angiotensin System Blockers on Glomerular Filtration Rate in Patients With Hypertension, Type 2 Diabetes With Normoalbuminuria
Information source: Hospital Authority, Hong Kong
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes; Hypertensive Disease
Intervention: Renin-angiotensin system blockers (Drug); non-renin angiotensin system blockers (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Hospital Authority, Hong Kong Official(s) and/or principal investigator(s): Wai Sing, Daniel CHU, M.B.,B.S., Principal Investigator, Affiliation: Hospital Authority, Hong Kong
Overall contact: Louise Pun, Phone: 852+3553-3219, Email: pts856@ha.org.hk
Summary
Diabetes is the leading cause of chronic kidney disease in developed countries. About 30-40%
of patients with type 1 and type 2 diabetes mellitus will develop diabetic nephropathy.
Microalbuminuria is often used as an early predictor of diabetic nephropathy. Many studies
already demonstrated the renoprotective effect of Renin-angiotensin-system (RAS) blockers in
patients with varying degree of albuminuria, few studies focus on studying the decline in
glomerular filtration rate (GFR) among patients with normoalbuminuria. However a substantial
number of diabetic patients exist with sub-normal GFR without microalbumin excretion. From
literature, diabetes mellitus will have faster decline in GFR but the investigators do not
know whether such decline can be slowed down by the use of RAS blockers as compared with
other anti-hypertensive drugs. This Study investigate the effect of early treatment with RAS
blockers on the decline rate of GFR in diabetic patients with normoalbuminuria.
Clinical Details
Official title: Phase IV, Effect of Rennin-Angiotensin System Blockers on Glomerular Filtration Rate in Patients With Hypertension, Type 2 Diabetes With Normoalbuminuria--- A Randomized Controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: change of estimated GFR calculated by MDRD equation and onset of microalbuminuria
Detailed description:
Renal excretory function, represented by GFR, deteriorates with age. After age 20-30 years,
GFR declines by 1ml/min per year. This age related loss of renal function is proportional to
blood pressure and glycemic level, and the rate of decline can accelerate up to 10-12 ml/min
per year in poor BP and glycemia control.(1) Such rate of deterioration may lead to
end-stage renal failure and the need for dialysis or transplantation.
Chronic kidney disease (CKD) is defined as either presence of kidney damage or GFR< 60
ml/min/1. 73 m2 for more than 3 months. Kidney damage is defined as pathological
abnormalities or markers of damage, including abnormalities in blood or urine tests or
imaging studies. Microalbuminuria is often an early and sensitive marker of kidney damage in
many types of chronic kidney disease. Among patients with chronic kidney disease, the stage
is divided into stage 1-5 by the level of GFR, with higher stages representing lower GFR
levels.(2) Renin-Angiotensin System ( RAS) is an enzymatic cascade in which angiotensinogen
is cleaved by renin to form angiotensin I, which in turn, is converted by angiotensin
converting enzyme (ACE) to form angiotensin II. Angiotensin II produces renal
vasoconstriction, so blocking the RAS is shown to be a useful approach to reduce the
renovascular risk. Among the RAS blocking agents, angiotensin converting enzyme inhibitor
(ACEI) and angiotensin receptor blockers (ARB) are most commonly used in clinical practice.
Many studies already demonstrated the renoprotective effect of ACEI and ARB. These studies
include MicroHOPE study(3), IRMA(4), IDNT(5), RENNAL(6) with subjects having varying degree
of albuminuria. With compelling benefit of RAS blockers in diabetic patients with
albuminuria, current guideline from American diabetic Association (ADA) recommend the use of
ACEI and ARB to delay the progression of renal disease in diabetic nephropathy.(7) According
to the National Kidney Foundation guideline, the workgroup recommend hypertensive patients
with diabetes and CKD stage 1-4 should be treated with an ACEI or ARB, usually in
combination with a diuretic.(8) For patients with suboptimal GFR (>= 60 ) without evidence
of kidney damage like microalbuminuria, they are not considered as having CKD. There is lack
of consensus on the selection of anti-hypertensive medication in this group of patients.
For subjects having normoalbuminuria, BENEDICT study demonstrates the delay in onset of
microalbuminuria with the use of either trandolapril alone or trandolapril plus
verapamil.(9) In ADVANCE trial, treatment with fixed combination of perindopril and
indapamide reduced total renal event by 21%, defined as having new or worsening nephropathy
or the development of new microalbuminuria.(10) However these studies mainly focus on using
urinary albumin excretion as outcome measures. They seldom took the value of GFR into
account.
However studies have found that significant decline in GFR in the absence of increase urine
albumin excretion exists in a substantial percentage of adults with diabetes.(11) Decline in
GFR should have diagnostic and prognostic value equivalent to urinary albumin excretion.
However from literature, we cannot found the effect of RAS blockers on the decline in GFR.
We therefore would like to carry out this study to investigate whether RAS blockers can
delay the progress of renal disease, with particular attention to the value of GFR, in
patients with GFR>=60 but without microalbuminuria.
Eligibility
Minimum age: 35 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion criteria:
1. Age >=35 - 80 years old who is capable to give consent
2. Chinese
3. Either (i) Type 2 DM diagnosed according to ADA guideline or (ii) Hypertension
defined as systolic blood pressure >140 or diastolic >90 mmHg or taking
anti-hypertensive medication to attain blood pressure under these level or having
(i) and (ii)
4. Estimated GFR (eGFR) (based on blood test taken 3 months prior to the date of
consent) 60 - 89 ml/min/1. 73m2 calculated by the abbreviated 4 variable Modification
of Diet in Renal Disease (MDRD) study equation and no other identified causes of
renal insufficiency.
5. Normoalbuminuria determined by urine albumin to creatinine ratio (based on urine test
taken 3 months prior to the date of consent) <2. 5 mg/mmol for men or <3. 5 mg/mmol for
women in first morning void urine sample.
Exclusion criteria:
1. Patients currently on ACEI or ARB as their anti-hypertensive medication
2. Pregnancy
3. Type 1 diabetes
4. Non-diabetic renal disease including renal artery stenosis
5. Secondary hypertension
6. History of symptomatic heart failure
7. History of myocardial infarction within 6 months
8. Specific indication for or contraindication to use ACEI or ARB
9. History of allergy to ACEI or ARB
Locations and Contacts
Louise Pun, Phone: 852+3553-3219, Email: pts856@ha.org.hk
Hospital Authority, HKEC, FM&PHC, Hong Kong, China; Recruiting Louise PUN, Phone: 852+3553-3219, Email: pts856@ha.org.hk Wai Sing, Daniel CHU, M.B.,B.S., Principal Investigator
Additional Information
Starting date: November 2011
Last updated: April 17, 2015
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