Clinical trial NCT04364139: African American Study of Kidney Disease and Hypertension
Official title: African American Study of Kidney Disease and Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertensive Nephrosclerosis
Chronic Renal Insufficiency
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: The Cleveland Clinic
First posted: 2020-04-27
Enrollment: 1094
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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).

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of change in GFR
timeFrame: Up to 3 years
Secondary outcomes:
measure: Time to 50% reduction in GFR, ESRD, or death up to 3 years
timeFrame: Up to 3 years
measure: Change in proteinuria
timeFrame: Baseline to 3 years
measure: Time to 50% reduction in GFR, ESRD, or death up to 10 years
timeFrame: Up to 10 years
Other outcomes:
Locations:
Study officials:
affiliation: CLEVELAND CLINIC LERNER COM-CWRU
name: JENNIFER GASSMAN
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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, 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.
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 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.