Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol.

BACKGROUND: Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown. METHODS/DESIGN: The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating. DISCUSSION: Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01120028 and ISRCTN88894088.

Effects of internet-based tailored advice on the use of cholesterol-lowering interventions: a randomized controlled trial.

BACKGROUND: Elevated low-density lipoprotein (LDL) cholesterol is a leading risk factor for cardiovascular disease. Despite the availability of proven interventions to lower LDL cholesterol, their use remains subobtimal. Many websites provide interactive, tailored advice on cardiovascular risk in an attempt to help bridge this evidence-practice gap, yet there is little evidence that provision of such a tool is effective in changing practice. OBJECTIVES: The objective was to define the effects on use of cholesterol-lowering interventions of a consumer-targeted tailored advice website. METHODS: This was a prospective, double-blind, randomized controlled trial open to any adult Australian with access to the Internet. A total of 2099 participants were randomized. Of these, 45% were male, the mean age of all participants was 56, and 1385 (66%) self-reported hypercholesterolemia. Follow-up information was obtained for 1945 (93%). Participants completed a brief online questionnaire. Individuals assigned to intervention received immediate, fully automated, personally tailored advice (based on current guidelines) regarding the need for commencement of statin therapy, increased statin therapy in those already on treatment, and nondrug intervention strategies. Control group participants were directed to static Web pages providing general information about cholesterol management. RESULTS: The primary outcome was the proportion of participants that commenced or increased use of prescribed cholesterol-lowering therapy. Of the total 2099 randomized participants, 304 (14%) met eligibility criteria for cholesterol-lowering therapy but were not prescribed treatment, and 254 (12%) were prescribed treatment but were not achieving the recommended target level. Treatment was commenced or increased in 64 (6.0%) of the 1062 intervention group participants and 79 (7.6%) of the 1037 control group participants (% difference = -1.6%, 95% confidence interval [CI] -3.75 to 0.57, P = .15). No differences were found between the randomized groups for the secondary outcomes of "discussed treatment with a health professional" (% difference = -3.8%, 95% confidence interval [CI] -8.16 to 0.19, P = .08), "had their cholesterol checked" (% difference = -1.5%, 95% CI -5.79 to 2.71, P = .48), "had their blood pressure checked" (% difference = 1.4%, 95% CI -2.55 to 5.34, P = .49) or made a lifestyle change (P values between .49 and .96). CONCLUSIONS: Despite providing specific carefully tailored advice, this website had no detectable effect on cholesterol management strategies. This finding raises considerable uncertainty about the value of Internet-based tools providing tailored advice directly to consumers. TRIAL REGISTRATION: NCT00220974; http://clinicaltrials.gov/ct2/show/NCT00220974 (Archived by WebCite at http://www.webcitation.org/5sdq63rrY).

A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial.

Timely participant recruitment remains a significant challenge for most clinical trials. We evaluated the effects on participant recruitment of communication between the central trial coordinators and the clinical sites in the setting of a large international multi-centre clinical trial. The effects of communication were determined in a single-blind randomised controlled trial involving 167 clinical sites in 19 countries. Clinical sites were randomised to either additional or usual communication strategies - the additional communication group received a communication package based on additional, individually-tailored feedback about recruitment, in addition to the usual correspondence from the central trial coordinators that was provided to the control group. The two study outcomes were the median time to half randomisation target and the median total number of participants randomised per clinical site. Eighty-five clinical centres were randomised to receive additional communication and 82 to receive usual communication. At the conclusion of recruitment, there was no significant difference in the median number of participants randomised per centre between the additional and usual groups (37.5 vs. 37.0, p=0.68). The median time to half randomisation target was lower in the additional communication group compared to the usual group, however this difference did not achieve conventional levels of statistical significance (4.4 months vs. 5.8 months, p=0.08). The findings suggest that the additional communication strategy may be of some incremental benefit in helping sites achieve recruitment targets sooner.

The effects on saturated fat purchases of providing internet shoppers with purchase- specific dietary advice: a randomised trial.

OBJECTIVES: The supermarket industry now services many customers through online food shopping over the Internet. The Internet shopping process offers a novel opportunity for the modification of dietary patterns. The aim of this study was to evaluate the effects on consumers' purchases of saturated fat of a fully automated computerised system that provided real-time advice tailored to the consumers' specific purchases recommending foods lower in saturated fat. DESIGN: This study was a blinded, randomised controlled trial. SETTING: The study was conducted in Sydney, New South Wales, Australia. PARTICIPANTS: The participants were consumers using a commercial online Internet shopping site between February and June 2004. INTERVENTIONS: Individuals assigned to intervention received fully automated advice that recommended specific switches from selected products higher in saturated fat to alternate similar products lower in saturated fat. Participants assigned to control received general non-specific advice about how to eat a diet lower in saturated fat. OUTCOME MEASURES: The outcome measure was the difference in saturated fat (grams per 100 g of food) in shopping baskets between the intervention and control groups. RESULTS: There were 497 randomised participants, mean age 40 y, each shopping for an average of about three people. The amount of saturated fat in the foods purchased by the intervention group was 0.66% lower (95% confidence interval 0.48-0.84, p < 0.001) than in the control group. The effects of the intervention were sustained over consecutive shopping episodes, and there was no difference in the average cost of the food bought by each group. CONCLUSIONS: Fully automated, purchase-specific dietary advice offered to customers during Internet shopping can bring about changes in food purchasing habits that are likely to have significant public health implications. Because implementation is simple to initiate and maintain, this strategy would likely be highly cost-effective.