African American Study of Kidney Disease and Hypertension

Chronic Renal Insufficiency Clinical Trial

— AASK  

Official title:

African American Study of Kidney Disease and Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04364139
• Other study ID #: AASK U01DK048648
• Secondary ID: U01DK048648
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 1995
• Est. completion date: June 30, 2007

Study information

• Verified date: April 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The AASK is a multicenter, randomized, controlled clinical trial using a 2 × 3 factorial design to evaluate the effects of level of blood pressure control and type of anti-hypertensive medication on progression of chronic renal disease among African American men and women with chronic renal insufficiency caused by hypertension (hypertensive nephrosclerosis).

Description:

The AASK is a multicenter, randomized, controlled clinical trial using a 2 × 3 factorial design to evaluate the effects of level of blood pressure control and type of anti-hypertensive medication on progression of chronic renal disease among African American men and women with chronic renal insufficiency caused by hypertension (hypertensive nephrosclerosis). Two levels of blood pressure control were defined in terms of mean arterial pressure (MAP = 2/3 diastolic blood pressure + 1/3 systolic blood pressure). A usual goal is defined as an MAP of 102 to 107 mm Hg, and a low goal is defined as an MAP of 92 mm Hg or less. The three antihypertensive drug regimens contained either a calcium channel blocker (amlodipine), β-blocker (metoprolol; Toprol XL), or angiotensin-converting enzyme inhibitor (ramipril) as initial therapy. Progression of renal disease was measured as the rate of decline in glomerular filtration rate (GFR).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1094
• Est. completion date: June 30, 2007
• Est. primary completion date: September 30, 2001
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. African-American men and women (including black individuals born in the Caribbean, Africa, Canada, etc.) age 18 to 70 years. Each center will attempt to include equal numbers of men and women, at least 1:3 of each.

2. Hypertension is defined as a sitting diastolic BP of 95 mmHg or more. The average of the last two of three consecutive readings on a random zero sphygmomanometer machine at any visit is the level used. Hypertensive participants on anti-hypertensive therapy at Baseline need only one qualifying clinic visit. Those not currently on medications at Baseline must qualify on each of two consecutive clinic visits.

3. Reduced renal function, defined as a prerandomization (G1 visit) 125I-iothalamate GFR between 20 to 65 ml/min 1.73 per m^2.

4. Willingness and ability to cooperate with the protocol.

Exclusion Criteria:

1. History of malignant or accelerated hypertension within 6 mo prior to study entry; previous chronic peritoneal or hemodialysis or renal transplantation.

2. Known secondary causes of hypertension.

3. Any known history of diabetes mellitus type I and II, or fasting (8-12 h) glucose >140 mg/dl on two occasions, or glucose >200 mg/dl on one occasion prior to randomization.

4. A ratio of urinary protein (mg/dl) to creatinine (mg/dl) exceeding 2.5 in a 24-h urine sample collected shortly before the initial GFR visit. (This ratio is used as an estimate of > 2.5 g/d proteinuria without needing to factor for validity of the collection.)

5. Clinical or renal biopsy evidence of any renal disease other than hypertensive nephrosclerosis. Persons with arteriographically documented renal arterial atherosclerotic disease less than 50% stenosis of the renal artery should be considered eligible for study participation if the principal investigator at the center feels the disease is not clinically significant.

6. History of drug abuse in the past 2 yr, including narcotics, cocaine, or alcohol (>21 drinks/wk).

7. Serious systemic disease that might influence survival or the course of renal disease. (Chronic oral steroid therapy is an exclusion, but steroid-containing nasal sprays are not. In active sarcoidosis is not an exclusion.)

8. Clinical evidence of lead intoxication.

9. Arm circumference >52 cm, which precludes measuring blood pressure with the "thigh" blood pressure cuff. Arm length such that if the cuff that is appropriate for the arm circumference extends into the antecubital space so that the cuff would interfere with placement of the stethoscope over the brachial artery for blood pressure measurement.

10. Clinical evidence of congestive heart failure, current or within the preceding 6 mn. Ejection fraction below 35% measured by any method. Heart block greater than first degree or any other arrhythmia that would contraindicate the use of any of the randomized drugs.

11. Reactive airway disease, current or in the preceding 6 mo requiring prescribed treatment for more than 2 wk.

12. Impairment or difficulty in voiding, precluding adequate urine collections.

13. Intake of nonsteroidal anti-inflammatory agents (NSAIDs) more than 15 d/mo, excluding aspirin. Inability to discontinue NSAIDs or aspirin for 5 d prior to GFR measurement.

14. History of severe adverse reaction to any of the randomized drugs required for use in the protocol or contraindication of their use.

15. Pregnancy or likelihood of becoming pregnant during the study period; lactation.

16. Serum potassium level >5.5 mEq/L at the study visit 2 (SV2) and confirmed at G1 for those not on ACE inhibitors during baseline, or serum potassium level >5.9 mEq/L at the SV2 and confirmed at G1 for those on ACE inhibitors during baseline.

17. Leukopenia <2,500/mm3 at SV2 and confirmed at the end of baseline.

18. Medically indicated need for any of the randomized drugs for any other reason (including angina pectoris, migraine, arrhythmia).

19. Allergy to iodine.

20. Suspicion that the participant will not be able to adhere to medications or comply with the protocol visit schedule.

21. Participation in another intervention study.

Related Conditions & MeSH terms

• Chronic Renal Insufficiency
• Hypertension
• Hypertensive Nephrosclerosis
• Kidney Diseases
• Nephrosclerosis
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Other:
• MAP goal less than or equal to 92 mm Hg
Lower Blood Pressure Goal (mean arterial pressure (MAP) less than or equal to 92 mm Hg) which corresponds to a BP of approximately 115/80 mmHg
• MAP goal 102-107 mm Hg
Usual Blood Pressure Goal (mean arterial pressure (MAP) 102-107 mm Hg) which corresponds to a BP of approximately 135/85 to 140/90 mmHg

Drug:
• Ramipril
An angiotensin-converting enzyme inhibitor, (ACEI: ramipril) 2.5 to 10 mg/d
• Amlodipine
A dihydropyridine calcium channel blocker, (DHPCCB: amlodipine) 5 to 10 mg/d
• Metoprolol
A sustained release beta-blocker, (BB: metoprolol) 50 to 200 mg/d

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	The Cleveland Clinic

References & Publications (3)

Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP, Charleston J, Cheek D, Cleveland W, Douglas JG, Douglas M, Dowie D, Faulkner M, Gabriel A, Gassman J, Greene T, Hall Y, Hebert L, Hiremath L, Jamerson K, Johnson CJ, Kopple J, Kusek J, Lash — View Citation

Appel LJ, Wright JT Jr, Greene T, Agodoa LY, Astor BC, Bakris GL, Cleveland WH, Charleston J, Contreras G, Faulkner ML, Gabbai FB, Gassman JJ, Hebert LA, Jamerson KA, Kopple JD, Kusek JW, Lash JP, Lea JP, Lewis JB, Lipkowitz MS, Massry SG, Miller ER, Norr — View Citation

Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, Cheek D, Douglas-Baltimore JG, Gassman J, Glassock R, Hebert L, Jamerson K, Lewis J, Phillips RA, Toto RD, Middleton JP, Rostand SG; African American Study of Kidney Disease and Hyperten — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of change in GFR	GFR slope was determined separately during the first 3 months after randomization (acute phase) and during the remainder of follow-up (chronic phase)	Up to 3 years
Secondary	Time to 50% reduction in GFR, ESRD, or death up to 3 years	Time from randomization to any of the following (1) confirmed reduction in GFR by 50% or by 25 mL/min per 1.73 m^2, (2) end stage renal disease (ESRD), or (3) death	Up to 3 years
Secondary	Change in proteinuria	Change in proteinuria from baseline to the end of follow-up	Baseline to 3 years
Secondary	Time to 50% reduction in GFR, ESRD, or death up to 10 years	Time from randomization to any of the following (1) confirmed reduction in GFR by 50% or by 25 mL/min per 1.73 m^2, (2) end stage renal disease (ESRD), or (3) death	Up to 10 years