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

This study has been completed.
Sponsor:
Information provided by:
Janssen-Cilag B.V.
ClinicalTrials.gov Identifier:
NCT00446576
First received: March 12, 2007
Last updated: January 31, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Anemia
Drug: Epoetin Alfa
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag B.V.:

Primary Outcome Measures:
  • Absolute change in left ventricular mass index

Secondary Outcome Measures:
  • 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

Enrollment: 176
Study Start Date: November 1999
Study Completion Date: April 2003
Detailed 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

  Eligibility

Ages Eligible for Study:   18 Years to 73 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00446576

Sponsors and Collaborators
Janssen-Cilag B.V.
Investigators
Study Director: Janssen-Cilag B.V. Clinical Trial Janssen-Cilag B.V.
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00446576     History of Changes
Other Study ID Numbers: CR005599
Study First Received: March 12, 2007
Last Updated: January 31, 2011
Health Authority: Netherlands: Netherlands Medicines Evaluation Board

Keywords provided by Janssen-Cilag B.V.:
Anemia
early renal insufficiency

Additional relevant MeSH terms:
Anemia
Renal Insufficiency
Hypertrophy, Left Ventricular
Hematologic Diseases
Kidney Diseases
Urologic Diseases
Cardiomegaly
Heart Diseases
Cardiovascular Diseases
Hypertrophy
Pathological Conditions, Anatomical
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014