The Effect of Epoetin Alfa on Cardiac Function and Quality of Life in Patients With Early Renal ((Kidney) Disease

Anemia Clinical Trial

Official title:

A Study in Early Renal Insufficiency Patients to Assess the Effect of Maintaining Three Different Hemoglobin Levels With the Use of Erythropoetin Alpha on Left Ventricular Hypertrophy and Dilation and Quality if Life; The "Cardiac Results of Early Treatment of Anaemia (CRETA)" Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00446576
• Other study ID #: CR005599
• Status: Completed
• Phase: Phase 3
• First received: March 12, 2007
• Last updated: January 31, 2011
• Start date: November 1999
• Est. completion date: April 2003

Study information

• Verified date: January 2011
• Source: Janssen-Cilag B.V.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Netherlands Medicines Evaluation Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess whether maintaining hemoglobin (Hb) levels at normal or sub-normal levels with Epoetin Alfa can influence the health status, left ventricular mass and quality of life of early renal insufficiency subjects without additional safety concerns.

Description:

The use of Epoetin alfa in the treatment of anaemia in chronic renal failure (CRF) patients is well accepted. The severity of anaemia in CRF patients increases with the degree of renal dysfunction. Thus, the most severe degree of anaemia is generally found in patients with end stage renal disease who must be maintained on dialysis. Nevertheless, a significant number of early renal insufficiency patients are also seen to be anaemic.

Most patients in Europe with end stage renal disease are maintained at an Hb level between 6 and 8 mmol/l. According to a survey during the second European Epoetin symposium (Creta, 1998) only 20% is maintained at Hb = 8 mmol/l, but most are maintained at values lower than 8 mmol/l. Even about 40% was maintained at Hb = 6 mmol/l.

A number of studies have found a relationship between left ventricular hypertrophy and haemoglobin in dialysis and pre-dialysis patients. Also a relation between LVH and morbidity and mortality has been found. For this reason it should be a suggestion to treat anaemia towards a higher level.

To treat Hb to a higher level a choice can be made to correct Hb when it has dropped to a very low level after renal disease has reached an advanced stage or alternatively to prevent anaemia in an early stage of renal disease. In an analysis of the normal hematocrit trial, Macdougall and Ritz suggest the latter. This is the main purpose of this trial.

Treatment with Epoetin alfa also makes patients feel better physically when their exercise capacity improves. During treatment with Epoetin alfa, several secondary effects may simultaneously influence the maximal exercise capacity after correction of the anaemia. The improved well-being may result in an increase in physical activity and exercise capacity can be further improved by such conditioning. The improved oxygen transport after correction of anaemia reverses the circulatory adaptation to hypoxia and most studies have shown a decrease in cardiac output at rest, and an increase in peripheral resistance. However, approximately one-third of chronic renal failure patients treated with Epoetin alfa have episodes of hypertension, and may require increased doses of anti-hypertensive medication.

This prospective study will assess whether maintaining Hb levels at normal or sub-normal levels can influence the health status, left ventricular mass and quality of life (QoL) of early renal insufficiency subjects without additional safety concerns. The patients will receive Epoetin Alfa as subcutaneous or intravenous injections in variable dosages for a maximum of 42 months

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: April 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 73 Years

Eligibility

Inclusion Criteria:

• Patients with early renal insufficiency who are not on haemodialysis

• A baseline Hb level of >7.5 mmol/l (120 g/l) but expected to decrease during the coming months. Allowed exceptions: Hb < 7,5 mmol/l (120 g/l) for a maximum of 6 months. In medical history an Hb < 7,0 mmol/l (113 g/l) is only allowed for a maximum period of 3 months and in relation to an accidental drop in Hb (f.e. caused by surgery, gastric bleeding etc.)

• Age: 18 - 73 years, given that patients >70 years are in good general condition and are expected to complete the 30 months study period

• Creatinine clearance < 40 ml/min/1.73 m2 (Cockcroft formula) or creatinin clearance < 50 ml/min/1.73 m2), given that the clearance and Hb show a downward tendency as demonstrated in the patient files and medical history

Exclusion Criteria:

• Presence of clinically significant disease/dysfunction of hepatic, pulmonary, hematological (e.g. sickle cell anaemia, thalassemia, major myelodysplastic syndromes, hemolytic anaemia), neurological, musculo-skeletal, endocrine, gastrointestinal or genitourinary system unrelated to underlying chronic renal failure which in the opinion of the investigator would disqualify the patient from this study

• Cystic kidney disease

• Clinical or laboratory evidence of untreated iron, folate or Vitamin B12 deficiency

• Presence of concomitant malignancy (other than basal cell carcinoma of the skin)

• Uncontrolled hypertension (i.e. diastolic blood pressure of > 100 mm Hg)

• History of seizures

• Administration of medication known to suppress erythropoiesis (e.g. cytotoxic agents, immuno-suppressive) within one month prior to enrolment. Low dose steroid therapy will be permitted

• Pregnancy or lactation

• Known hypersensitivity to Epoetin alfa or one of its components.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Renal Insufficiency

Intervention

Drug:
• Epoetin Alfa

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag B.V.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change in left ventricular mass index
Secondary	Incidence of Left Ventricular hypertrophy QoL assessment (FACIT-Fatigue Scale and KDQOL-SFÒ) The change in pulse pressure during the study period. Morbidity and mortality during the study-period Deterioration of renal function Days in hospital