52A Effectiveness of a placebo run-in period in increasing the power of a chemoprevention trial, CARET

Abstract

Objective: The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg β-carotene and 25 000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with β-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result. Methods: Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination. Results: Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters. Conclusion: Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.