Clinical trial NCT03195023: Effect of RAS Blockers on CKD Progression in Elderly Patients With Non Proteinuric Nephropathies (PROERCAN01)
Official title: Effect of Renin-angiotensin-system (RAS) Blocker Drugs on Chronic Kidney Disease (CKD) Progression in Elderly Patients With Non Proteinuric Nephropathies (PROERCAN01)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Renal Insufficiency, Chronic
Proteinuria
Keywords: Renal insufficiency, Chronic
Lead sponsor: Hospital General Universitario Gregorio Marañon
Sponsor class: OTHER
First posted: 2017-06-22
Enrollment: 106
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect of renin-angiotensin blockers on chronic kidney disease progression in elderly (\>65 years old) patients with non-proteinuric nephropathies. Half of the patients will receive angiotensin converting enzyme inhibitors, while the other half will not receive them. Renal function, proteinuria and cardiovascular events will be follow up during a three year period.

Detailed description: STUDY DESIGN: Open, multicentre, prospective, parallel-group, randomized controlled study comparing the effect of an angiotensin converting enzyme inhibitor (ACEI) vs standard antihypertensive treatment without ACEI, in the progression of renal disease in elderly patients with non-proteinuric 3-4 stage chronic renal disease.

Elderly patients (\> 65 years) with moderate-severe non-proteinuric chronic renal disease (estimated Glomerular Filtrate Rate between 19-59 ml per minute per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration Group equation) and urine-creatinine rate \< 30 mg/g, will be included. They will be randomly assigned in a 1:1 ratio to receive ACEI or standard antihypertensive treatment. Patients will be followed up for 3 years.

Eligibility criteria: Inclusion Criteria:

* Age \>65 years
* Chronic kidney disease stage 3 or 4 (GFR measured by CKD-EPI 15-59 ml/min/1,73 m2)
* Albumine/creatinine index \< 30 mg/g in simple urine sample or albuminuria \< 30 mg/day in 24-hour urine sample.
* Previous hypertensive treatment::

  1. patients who have not received RAS blockers in the three months prior to inclusion can be included
  2. patients who are receiving RAS blockers could be included after one month washout period

Exclusion Criteria:

* Diabetes mellitus (type 1 or 2)
* Glomerulopathy
* Chronic heart failure or coronary heart disease
* Poorly controlled hypertension (\>160/100 mmHg)
* Monorrenal
* Active malignant neoplasia (except skin cancer different from melanoma). Patients who have been free of malignancy for the last 5 years could be included.
* Chronic symptomatic or not controlled inflammatory disease (eg rheumatoid arthritis, Chron disease, ulcerative colitis or systemic lupus erythematosus)
* Chronic liver disease
* Allergy or intolerance to renin angiotensin system blockers or calcium channel blockers
* Hepatitis B, C or HIV infection
* Immunosuppressive treatment in the 3 months prior to inclusion
* Hospitalization of any cause in the three months prior to inclusion
* Rapidly progressive kidney disease (decline in GFR \>5ml/min/1.73 m2/year)
* Inability to sign the informed consent

Primary outcomes:
measure: Chronic kidney disease progression
timeFrame: 3 years
Secondary outcomes:
measure: Security of RAS blockers in elderly patients
timeFrame: 3 years
measure: Security of RAS blockers in elderly patients
timeFrame: 3 years
measure: Effect of RAS blockers on mortality in elderly patients
timeFrame: 3 years
measure: Effects of RAS blockers on cardiovascular risk in elderly patients
timeFrame: 3 years
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Gregorio Maranon Hospital
Study officials:
affiliation: Hospital General Universitario Gregorio Marañon
name: Maria Angeles Goicoechea, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE, de Zeeuw D, Shahinfar S, Toto R, Levey AS; AIPRD Study Group. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003 Aug 19;139(4):244-52. doi: 10.7326/0003-4819-139-4-200308190-00006.
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.
citation: O'Hare AM, Kaufman JS, Covinsky KE, Landefeld CS, McFarland LV, Larson EB. Current guidelines for using angiotensin-converting enzyme inhibitors and angiotensin II-receptor antagonists in chronic kidney disease: is the evidence base relevant to older adults? Ann Intern Med. 2009 May 19;150(10):717-24. doi: 10.7326/0003-4819-150-10-200905190-00010.
citation: Ahmed AK, Kamath NS, El Kossi M, El Nahas AM. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. Nephrol Dial Transplant. 2010 Dec;25(12):3977-82. doi: 10.1093/ndt/gfp511. Epub 2009 Oct 10.
citation: Weiss JW, Thorp ML, O'Hare AM. Renin-angiotensin system blockade in older adults with chronic kidney disease: a review of the literature. Curr Opin Nephrol Hypertens. 2010 Sep;19(5):413-9. doi: 10.1097/MNH.0b013e32833b8d6b.
citation: Turgut F, Balogun RA, Abdel-Rahman EM. Renin-angiotensin-aldosterone system blockade effects on the kidney in the elderly: benefits and limitations. Clin J Am Soc Nephrol. 2010 Jul;5(7):1330-9. doi: 10.2215/CJN.08611209. Epub 2010 May 24.