Outlook: Clinical Trials

Pharmacy TimesJune 2011 Women's Health
Volume 77
Issue 6

Treatment of Nonalcoholic Fatty Liver Disease in Children And Adolescents

A recent clinical trial was conducted to determine whether children with nonalcoholic fatty liver disease (NAFLD) would benefit from therapeutic intervention with vitamin E or metformin. 3 This randomized, double-blind, double-dummy, placebo-controlled clinical trial evaluated 173 patients between the ages of 8 and 17 years with NAFLD, confirmed with biopsy.

Study subjects received 800 IU of vitamin E (n = 58), 1000 mg of metformin (n = 57), or placebo (n = 58) for a total of 96 weeks. The primary end point of the study was sustained reduction in alanine aminotransferase (ALT)—defined as 50% or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment. Secondary end points included improvements in histological features of NAFLD and resolution of nonalcoholic steatohepatitis (NASH).

Study results demonstrated that sustained ALT reduction in the metformin group (16%; 95% CI, 7% to 28%; P = .83) and vitamin E group (26%; 95% CI, 15%-39%; P = .26) was similar to that of the placebo group (17%; 95% CI, 9%-29%). Additionally, the proportion of patients with NASH who resolved at 96 weeks was 28% with placebo (95% CI, 15%-45%) versus 58% with vitamin E (95% CI, 42%-73%; P = .006) and 41% with metformin (95% CI, 26%-58%; P = .23). Investigators concluded that neither vitamin E nor metformin was more effective than placebo in achieving the primary end point.

Leukotriene Antagonist Treatment for Asthma

Two parallel, multicenter, pragmatic trials evaluated the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta 2 -agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. 4

The study included primary care patients aged 12 to 80 years with impaired asthmarelated quality of life as determined by a Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score ≤6 or inadequate asthma control as determined by an Asthma Control Questionnaire (ACQ) score ≥1. Study subjects were randomized to receive open-label therapy with an LTRA (n = 148) or an inhaled glucocorticoid (n = 158) in the first-line controller therapy trial. Subjects in the add-on therapy trial received an LTRA (n = 170) or LABA (n = 182) added to an inhaled glucocorticoid.

Results showed that mean MiniAQLQ scores increased by 0.8 to 1.0 point over 2 years in both trials. Differences in the MiniAQLQ scores between the 2 treatment groups met investigators’ definition of equivalence (95% CI for an adjusted mean difference, -0.3 to 0.3) at 2 months. At 2 years, differences approached equivalence with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. There were no significant differences between the 2 groups in exacerbation rates and ACQ scores. PT

Effectiveness of Radical Prostatectomy in Early Prostate Cancer

A recently published study showed that the rate of death from prostate cancer was reduced in men who underwent radical prostatectomy, as compared with watchful waiting. 1 This report, which estimates 15-year results, looked at data from 695 men with early prostate cancer randomized to watchful waiting or radical prostatectomy from October 1989 through February 1999.

Results showed a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7% for the watchful waiting and radical prostatectomy groups, respectively. During a median of 12.8 years, 166 of the 347 men in the radical prostatectomy group and 201 of the 348 in the watchful waiting group died (P = .007).

The number needed to treat (NNT) to prevent 1 death was 15 overall. The NNT for men younger than 65 years was 7. Extracapsular tumor growth was a poor predictor of outcome among men who underwent radical prostatectomy—resulting in a 7-fold higher risk of death from prostate cancer compared with men without extracapsular tumor growth (relative risk, 6.9; 95% confidence interval [CI], 2.6 to 18.4).

Combination Phentermine Plus Topiramate Therapy for Weight Loss

A randomized, double-blind, 56-week, phase 3 trial—the CONQUER trial— evaluated the use of combination phentermine and topiramate therapy in overweight or obese adults (body mass index 27-45 kg/m2) with 2 or more comorbidities (n = 2487). 2 Comorbidities included hypertension, dyslipidemia, diabetes or prediabetes, and abdominal obesity.

Study subjects were randomized to receive once-daily phentermine 7.5 mg plus topiramate 46 mg (n = 498), oncedaily phentermine 15 mg plus topiramate 92 mg (n = 995), or placebo (n = 994). The primary end points of the study were the percentage change in body weight and the proportion of patients achieving at least 5% weight loss.

Study results showed that, at 56 weeks, change in body weight was -1.4 kg (leastsquares mean -1.2%, 95% CI -1.8 to -0.7) in the patients assigned to placebo, -8.1 kg (-7.8%, -8.5 to -7.1; P <.0001) in the phentermine 7.5 mg plus topiramate 46 mg group, and -10.2 kg (-9.8%, -10.4 to -9.3; P <.0001) in the phentermine 15 mg plus topiramate 92 mg group. Twenty-one percent of patients in the placebo group achieved at least 5% weight loss, compared with 62% and 70% in the phentermine 7.5 mg plus topiramate 46 mg and phentermine 15 mg plus topiramate 92 mg groups, respectively. Investigators concluded that the combination of phentermine and topiramate may be a valuable treatment for obesity.

Dr. Reed received her doctor of pharmacy degree from the University of the Sciences in Philadelphia, Pennsylvania, and currently works as a medical editor in the greater Philadelphia area.


1. Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011;364(18):1708-1717.

2.Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med. 2011;364(18):1695-1707.

3. Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305(16):1659-1668.

4. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341-1352.

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