Redesigning a large-scale clinical trial in response to negative external trial results: the CAMUS study of phytotherapy for benign prostatic hyperplasia.
BACKGROUND
Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are gaining popularity in the US. Two phytotherapies commonly used for BPH are extracts of the fruit of Serenoa repens, the Saw palmetto dwarf palm that grows in the Southeastern US, and extracts of the bark of Pygeum africanum, the African plum tree.


OBJECTIVE
The objective of the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) clinical trial is to determine if phytotherapy is superior to placebo in the treatment of BPH.


METHODS
CAMUS was originally designed as a 3300-participant, four-arm trial of S. repens, P. africanum, an alpha-adrenergic blocking drug, and placebo with time to clinical progression of BPH, a measure of long-term efficacy, as the primary endpoint. Before enrollment started, a randomized, double-blind, placebo-controlled, single institution clinical trial showed that S. repens at the usual dose did not demonstrate any benefit over placebo with respect to symptom relief at 1 year. Consequently, the focus of CAMUS shifted from evaluating long-term efficacy to determining if any short-term (6-18 months) symptom relief could be achieved with increasing doses of S. repens, the phytotherapy most commonly used in the US for BPH.


RESULTS
Results are anticipated in 2011.


CONCLUSIONS
Trial design occurs in an environment of continually evolving information. In this case, emerging results from another trial suggested that a study of long-term efficacy was premature, and that an effective dose and preparation of S. repens had to be established before proceeding to a long-term clinical trial.
Lee
Jeannette
J
Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. jylee@uams.edu
Andriole
Gerald
G
Avins
Andrew
A
Crawford
E David
ED
Foster
Harris
H
Kaplan
Steven
S
Kreder
Karl
K
Kusek
John
J
McCullough
Andrew
A
McVary
Kevin
K
Meleth
Sreelatha
S
Naslund
Michael
M
Nickel
J Curtis
JC
Nyberg
Leroy
L
Roehrborn
Claus
C
Dale Williams
O
O
Barry
Michael
M
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D008517:Phytotherapy / Q000379:methods*; D024301:Plant Bark; D010936:Plant Extracts; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D000068218:Prunus africana; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D028024:Serenoa
D000317:Adrenergic alpha-Antagonists; D010936:Plant Extracts