Outlook: Clinical Trials

JULY 11, 2011
Michele Reed, PharmD

Ovarian Cancer Screening and Effect on Mortality

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), a randomized, controlled trial, evaluated the effect of screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound. 1

The study evaluated 78,216 women aged 55 to 74 years. Study subjects underwent either annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years (n = 39,105) or usual care (n = 39,111). Subject follow-up for cancer diagnoses and death commenced for a maximum of 13 years (median = 12.4 years; range = 10.9-13.0 years) until February 28, 2010. The primary outcome of the study was mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers.

Results showed ovarian cancer diagnosis in 212 subjects (5.7 per 10,000 personyears) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). Ovarian cancer caused 118 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer; 76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06).

Investigators concluded that simultaneous screening with CA-125 and transvaginal ultrasound among women in the general US population did not reduce ovarian cancer mortality compared with usual care.

CeftrIaxone For Bacterial MenIngitis In Children

A recent multi-country, double-blind, placebo-controlled, randomized equivalence study evaluated 5- and 10-day treatments of ceftriaxone in children 2 months to 12 years of age with purulent meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type B, or Neisseria meningitidis. 2 Study subjects who were stable after 5 days of treatment were randomized to receive a further 5 days of ceftriaxone or placebo. The primary outcomes were bacteriologic failure or relapse. There were 2 relapses in the 5-day group and no relapses in the 10-day group.

There were no bacteriologic failures in either group. Investigators concluded that, in stable children 2 months to 12 years of age with purulent meningitis caused by these bacteria, ceftriaxone can be safely discontinued by the fifth treatment day.

Injectable Extended Release Naltrexone for OpIoId Dependence

A recent clinical trial assessed the efficacy, safety, and patient-reported outcomes of an injectable, oncemonthly, extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification. 3 This double-blind, placebo-controlled, randomized, 24-week trial evaluated patients with opioid dependence disorder. Study subjects were 18 years or older and had 30 days or less of inpatient detoxification and at least 7 days off all opioids. Subjects were randomly assigned (1:1) to either 380 mg XR-NTX (n = 126) or placebo (n = 124). Participants also received 12 biweekly counseling sessions. The primary end point was the response profile for confirmed abstinence during weeks 5 to 24, assessed by urine drug tests and self report of nonuse.

Study results demonstrated the median proportion of weeks of confirmed abstinence was 90.0% (95% CI, 69.9-92.4) in the XR-NTX group, compared with 35.0% (11.4-63.8) in the placebo group (P = .0002). Patients in the XR-NTX group self-reported a median of 99.2% (range = 89.1-99.4) opioidfree days, compared with 60.4% (46.2-94.0) for the placebo group (P = .0004). The mean change in craving was -10.1 (95% CI, -12.3 to -7.8) in the XR-NTX group, compared with 0.7 (–3.1 to 4.4) in the placebo group (P <.0001). Investigators concluded that XR-NTX, in conjunction with psychosocial treatment, might improve acceptance of opioid dependence pharmacotherapy and provide a useful treatment option for many patients.

Effects of IncreasIng the PrequIt MedIcatIon Period wIth Varenicline

A recent study evaluated smokers (n = 101) attending a stop-smoking clinic in London, United Kingdom.4 Study subjects were randomized to receive varenicline for 4 weeks before the target quit date (TQD) or placebo for 3 weeks before the TQD, followed by varenicline for 1 week before the TQD. Subjects in both groups received standard varenicline treatment for 3 months after the TQD. Study outcomes included smoking satisfaction and smoke intake before quitting, urges to smoke and withdrawal discomfort after quitting, and sustained abstinence from the TQD to 3 months.

Study results showed that 4 weeks of varenicline prior to the TQD reduced prequit enjoyment of smoking (P = .004) and smoke intake (P <.001), with 36.7% of participants reducing their cotinine concentrations by more than 50% (reducers). Varenicline preloading did not affect postquit withdrawal symptoms, but it increased 12-week abstinence rates (47.2% in the varenicline arm vs 20.8% in the placebo arm, P = .005). The effect was particularly strong among the reducers in the varenicline arm (66.7% in reducers vs 22.6% in nonreducers, P = .002). Additionally, varenicline preloading was well tolerated among study subjects. Investigators concluded that varenicline preloading can generate a substantial reduction in ad lib smoking and enhance 12-week quit rates.

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. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295-2303.

2. Molyneux E, Nizami SQ, Saha S, et al. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Lancet. 2011;377(9780):1837-1845.

3. Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506-1513.

4. Hajek P, McRobbie HJ, Myers KE, Stapleton J, Dhanji AR. Use of varenicline for 4 weeks before quitting smoking: decrease in ad lib smoking and increase in smoking cessation rates. Arch Intern Med. 2011;171(8):770-777.

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