African American Study of Kidney Disease and Hypertension

NCT04364139 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: AASK U01DK048648U01DK048648
• Study Type: interventional
• Target: 1,094
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Hypertensive Nephrosclerosis; Chronic Renal Insufficiency

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Time to 50% reduction in GFR, ESRD, or death up to 3 years

  Up to 3 years

• Change in proteinuria

  Baseline to 3 years

• Time to 50% reduction in GFR, ESRD, or death up to 10 years

  Up to 10 years

Study Arms (6)

Lower BP goal and Ramipril

EXPERIMENTAL

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; Drug: Ramipril

Usual BP goal and Ramipril

EXPERIMENTAL

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

Other: MAP goal 102-107 mm Hg; Drug: Ramipril

Lower BP goal and Amlodipine

EXPERIMENTAL

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; Drug: Amlodipine

Usual BP goal and Amlodipine

EXPERIMENTAL

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; Drug: Amlodipine

Lower BP goal and Metoprolol

EXPERIMENTAL

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; Drug: Metoprolol

Usual BP goal and Metoprolol

EXPERIMENTAL

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; Drug: Metoprolol

Interventions

MAP goal less than or equal to 92 mm Hg OTHER

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

Lower BP goal and Amlodipine; Lower BP goal and Metoprolol; Lower BP goal and Ramipril

MAP goal 102-107 mm Hg OTHER

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

Usual BP goal and Amlodipine; Usual BP goal and Metoprolol; Usual BP goal and Ramipril

Ramipril DRUG

An angiotensin-converting enzyme inhibitor, (ACEI: ramipril) 2.5 to 10 mg/d

Also known as: ACEI

Lower BP goal and Ramipril; Usual BP goal and Ramipril

Amlodipine DRUG

A dihydropyridine calcium channel blocker, (DHPCCB: amlodipine) 5 to 10 mg/d

Also known as: DHPCCB

Lower BP goal and Amlodipine; Usual BP goal and Amlodipine

Metoprolol DRUG

A sustained release beta-blocker, (BB: metoprolol) 50 to 200 mg/d

Also known as: BB

Lower BP goal and Metoprolol; Usual BP goal and Metoprolol

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Reduced renal function, defined as a prerandomization (G1 visit) 125I-iothalamate GFR between 20 to 65 ml/min 1.73 per m\^2.
• Willingness and ability to cooperate with the protocol.

You may not qualify if:

• History of malignant or accelerated hypertension within 6 mo prior to study entry; previous chronic peritoneal or hemodialysis or renal transplantation.
• Known secondary causes of hypertension.
• 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.
• 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.)
• 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.
• History of drug abuse in the past 2 yr, including narcotics, cocaine, or alcohol (\>21 drinks/wk).
• Clinical evidence of lead intoxication.
• 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.
• 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.
• Reactive airway disease, current or in the preceding 6 mo requiring prescribed treatment for more than 2 wk.
• Impairment or difficulty in voiding, precluding adequate urine collections.
• 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.
• History of severe adverse reaction to any of the randomized drugs required for use in the protocol or contraindication of their use.
• Pregnancy or likelihood of becoming pregnant during the study period; lactation.
• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• The Cleveland Clinic: collaborator

Related 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 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.

  PMID: 11386927 RESULT

• 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.

  PMID: 20818902 RESULT

• 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.

  PMID: 12435255 RESULT

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Ramipril; Amlodipine; Metoprolol

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• JENNIFER GASSMAN

  CLEVELAND CLINIC LERNER COM-CWRU

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators were masked to randomized drug but not BP goal
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 27, 2020
• Study Start: February 1, 1995
• Primary Completion: September 30, 2001
• Study Completion: June 30, 2007
• Last Updated: April 27, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR, ANALYTIC CODE