African American Study of Kidney Disease and Hypertension (AASK)

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).

Study Overview

• Status: Completed
• Conditions: Hypertensive Nephrosclerosis; Chronic Renal Insufficiency
• Intervention / Treatment: Other: MAP goal less than or equal to 92 mm Hg; Drug: Ramipril; Other: MAP goal 102-107 mm Hg; Drug: Amlodipine; Drug: Metoprolol

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 1094
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lower BP goal and Ramipril; Participants assigned to Lower Blood Pressure Goal (MAP less than or equal to 92 mm Hg) and Participants assigned to Receive Ramipril 2.5 to 10 mg/d	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; Drug: Ramipril; An angiotensin-converting enzyme inhibitor, (ACEI: ramipril) 2.5 to 10 mg/d; Other Names: ACEI
Experimental: Usual BP goal and Ramipril; Participants assigned to usual Blood Pressure Goal (MAP of 102 to 107 mm Hg) and participants assigned to Receive Ramipril 2.5 to 10 mg/d	Drug: Ramipril; An angiotensin-converting enzyme inhibitor, (ACEI: ramipril) 2.5 to 10 mg/d; Other Names: ACEI; Other: 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
Experimental: Lower BP goal and Amlodipine; Participants assigned to Lower Blood Pressure Goal (MAP less than or equal to 92 mm Hg) and Participants assigned to Receive Amlodipine 5 to 10 mg/d	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; Drug: Amlodipine; A dihydropyridine calcium channel blocker, (DHPCCB: amlodipine) 5 to 10 mg/d; Other Names: DHPCCB
Experimental: Usual BP goal and Amlodipine; Participants assigned to usual Blood Pressure Goal (MAP of 102 to 107 mm Hg) and Participants assigned to Receive Amlodipine 5 to 10 mg/d	Other: 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: Amlodipine; A dihydropyridine calcium channel blocker, (DHPCCB: amlodipine) 5 to 10 mg/d; Other Names: DHPCCB
Experimental: Lower BP goal and Metoprolol; Participants assigned to Lower Blood Pressure Goal (MAP less than or equal to 92 mm Hg) and Participants assigned to Receive Metoprolol 50 to 200 mg/d	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; Drug: Metoprolol; A sustained release beta-blocker, (BB: metoprolol) 50 to 200 mg/d; Other Names: BB
Experimental: Usual BP goal and Metoprolol; Participants assigned to usual Blood Pressure Goal (MAP of 102 to 107 mm Hg) and Participants assigned to Receive Metoprolol 50 to 200 mg/d	Other: 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: Metoprolol; A sustained release beta-blocker, (BB: metoprolol) 50 to 200 mg/d; Other Names: BB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in proteinuria	Change in proteinuria from baseline to the end of follow-up	Baseline to 3 years
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

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: The Cleveland Clinic
• Investigators: Principal Investigator: JENNIFER GASSMAN, CLEVELAND CLINIC LERNER COM-CWRU

Publications and helpful links

General Publications

• 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 J, Lea J, Lewis JB, Lipkowitz M, Massry S, Middleton J, Miller ER 3rd, Norris K, O'Connor D, Ojo A, Phillips RA, Pogue V, Rahman M, Randall OS, Rostand S, Schulman G, Smith W, Thornley-Brown D, Tisher CC, Toto RD, Wright JT Jr, Xu S; African American Study of Kidney Disease and Hypertension (AASK) Study Group. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA. 2001 Jun 6;285(21):2719-28. doi: 10.1001/jama.285.21.2719.
• 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, Norris K, Phillips RA, Pogue VA, Randall OS, Rostand SG, Smogorzewski MJ, Toto RD, Wang X; AASK Collaborative Research Group. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010 Sep 2;363(10):918-29. doi: 10.1056/NEJMoa0910975.
• 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 Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002 Nov 20;288(19):2421-31. doi: 10.1001/jama.288.19.2421. Erratum In: JAMA. 2006 Jun 21;295(23):2726.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 1995
• Primary Completion (Actual): September 30, 2001
• Study Completion (Actual): June 30, 2007

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Nephrosclerosis; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Protease Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Amlodipine; Metoprolol; Ramipril
• Other Study ID Numbers: AASK U01DK048648; U01DK048648 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data and samples are available at the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) Central Repository
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No