The health-related quality of life was not improved by targeting higher hemoglobin in the Normal Hematocrit Trial

Kidney Int. 2012 Jul;82(2):235-41. doi: 10.1038/ki.2012.76. Epub 2012 Mar 21.

Abstract

The Normal Hematocrit Trial (NHT) was the largest trial of epoetin randomizing 1265 hemodialysis patients with cardiac disease to lower (9-11 g/dl) or higher (13-15 g/dl) hemoglobin (Hgb), hypothesizing that higher Hgb would reduce mortality, and improve survival and quality of life. The trial was terminated early, and a 1998 publication reported that targeting higher hematocrit levels led to an insignificant increase in the primary end points (death or myocardial infarct), or risk ratio 1.3, 95% confidence interval (CI), 0.9-1.90, but the P-value was not given, and all-cause death risk was not reported. A higher target reportedly did not increase hospitalization rates, but did significantly improve the 'physical function' domain of quality of life. Comparing the 1996 Food and Drug Administration (FDA)-filed clinical trial report to the 1998 publication, however, found several discrepancies. Among these, the 1998 article reported interim trial results with only the adjusted CI but did not state that the unadjusted CIs were 99.912th percentile, and despite being a secondary end point, reported only the association of achieved Hgb with higher quality of life score. Randomization to the higher target had actually increased the risk for the primary end point (risk ratio 1.28, 95% CI=1.06-1.56; P=0.0112; 99.92% CI=0.92-1.78), the risk of death (risk ratio 1.27, 95% CI=1.04-1.54), non-access thrombotic events (P=0.041), and hospitalization rate (P=0.04), while 'physical function' did not improve (P=0.88). Hence, disclosure of these results in the 1998 publication or access to the FDA-filed report on the NHT in the late 1990s would likely have led to earlier concerns about epoetin safety and greater doubts about its benefits.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Access to Information
  • Anemia / blood
  • Anemia / diagnosis
  • Anemia / drug therapy*
  • Anemia / mortality
  • Anemia / psychology
  • Biomarkers / blood
  • Chi-Square Distribution
  • Early Termination of Clinical Trials
  • Emotions
  • Erythropoietin / adverse effects*
  • Evidence-Based Medicine
  • Health Status
  • Heart Diseases / blood
  • Heart Diseases / mortality
  • Heart Diseases / psychology
  • Heart Diseases / therapy*
  • Hematinics / adverse effects*
  • Hematocrit*
  • Hemoglobins / metabolism*
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Diseases / blood
  • Kidney Diseases / mortality
  • Kidney Diseases / psychology
  • Kidney Diseases / therapy*
  • Mental Health
  • Patient Safety
  • Practice Guidelines as Topic
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Quality of Life*
  • Renal Dialysis* / adverse effects
  • Renal Dialysis* / mortality
  • Risk Assessment
  • Risk Factors
  • Social Behavior
  • Time Factors
  • Treatment Outcome
  • United States

Substances

  • Biomarkers
  • Hematinics
  • Hemoglobins
  • Erythropoietin