Trials - Latest Articles

Standard abdominal wound edge protection with surgical dressings vs coverage with a sterile circular polyethylene drape for prevention of surgical site infections (BaFO): study protocol for a randomized controlled trial

Andre Mihaljevic — 2012-05-15T00:00:00Z

Background: Postoperative surgical site infections cause substantial morbidity, prolonged hospitalization, costs and even mortality and remain one of the most frequent surgical complications. Approximately 14% to 30% of all patients undergoing elective open abdominal surgery are affected and methods to reduce surgical site infection rates warrant further investigation and evaluation in randomized controlled trials. Methods: To investigate whether the application of a circular plastic wound protector reduces the rateof surgical site infections in general and visceral surgical patients that undergo midline or transverse laparotomy by 50%. BaFO is a randomized, controlled, patient-blinded andobserver-blinded multicenter clinical trial with two parallel surgical groups. The primary outcome measure will be the rate of surgical site infections within 45 days postoperativeassessed according to the definition of the Center for Disease Control. Statistical analysis of the primary endpoint will be based on the intention-to-treat population. The global level of significance is set at 5% (2 sided) and sample size (n = 258 per group) is determined to assurea power of 80% with a planned interim analysis for the primary endpoint after the inclusion of 340 patients.DiscussionThe BaFO trial will explore if the rate of surgical site infections can be reduced by a single,simple, inexpensive intervention in patients undergoing open elective abdominal surgery. Itspragmatic design guarantees high external validity and clinical relevance.Trial registrationhttp://www.clinicaltrials.gov NCT01181206. Date of registration: 11 August 2010; date offirst patient randomized: 8 September 2010.

Life- and person-centred help in Mecklenburg-Western Pomerania, Germany (DelpHi): study protocol for a randomised controlled trial

Jochen René Thyrian — 2012-05-10T00:00:00Z

Background: The provision of appropriate medical and nursing care for people with dementia is a major challenge for the healthcare system in Germany. New models of healthcare provision need to be developed, tested and implemented on the population level. Trials in which collaborative care for dementia in the primary care setting were studied have demonstrated its effectiveness. These studies have been conducted in different healthcare systems, however, so it is unclear whether these results extend to the specific context of the German healthcare system.The objective of this population-based intervention trial in the primary care setting is to test the efficacy and efficiency of implementing a subsidiary support system on a population level for persons with dementia who live at home.Methods and study designThe study was designed to assemble a general physician-based epidemiological cohort of people above the age of 70 who live at home (DelpHi cohort). These people are screened for eligibility to participate in a trial of dementia care management (DelpHi trial). The trial is a cluster-randomised, controlled intervention trial with two arms (intervention and control) designed to test the efficacy and efficiency of implementing a subsidiary support system for persons with dementia who live at home. This subsidiary support system is initiated and coordinated by a dementia care manager: a nurse with dementia-specific qualifications who delivers the intervention according to a systematic, detailed protocol. The primary outcome is quality of life and healthcare for patients with dementia and their caregivers. This is a multidimensional outcome with a focus on four dimensions: (1) quality of life, (2) caregiver burden, (3) behavioural and psychological symptoms of dementia and (4) pharmacotherapy with an antidementia drug and prevention or suspension of potentially inappropriate medication. Secondary outcomes include the assessment of dementia syndromes, activities of daily living, social support health status, utilisation of health care resources and medication.DiscussionThe results will provide evidence for specific needs in ambulatory care for persons with dementia and will show effective ways to meet those needs. Qualification requirements will be evaluated, and the results will help to modify existing guidelines and treatment paths.Trial registrationNCT01401582

INtimal hyPerplasia evAluated by oCT in de novo COROnary lesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO): study protocol for a randomized controlled trial

Francesco Burzotta — 2012-05-06T00:00:00Z

Background: Neointimal hyperplasia plays a pivotal role in the pathogenesis of in-stent restenosis inpatients undergoing percutaneous coronary interventions. Drug-eluting balloons are apromising tool to prevent restenosis after coronary angioplasty. Moreover, an increasedknowledge of the pathophysiology of restenosis my help improve therapeutic strategies. Methods: We present the design of an open-label, randomized three-arm clinical trial aimed to assesswhether a strategy of bare-metal stent implantation with additional use of drug-elutingballoons, either before (pre-dilation) or after stenting (post-dilation), reduces the primaryendpoint of in-stent neointimal hyperplasia area as compared with a strategy of bare-metalstent implantation alone. This primary endpoint will be assessed by optical coherencetomography at follow-up. Secondary endpoints will be the percentage of uncovered struts,and the percentage of struts with incomplete apposition. An ancillary study investigating therelation between systemic levels of endothelial progenitors cells and neointimal hyperplasia,and the interaction between endothelial progenitors cell levels and drug-eluting balloons hasbeen planned. Thirty consecutive patients undergoing percutaneous coronary interventionwill be randomized with a 1:1:1 design to bare-metal stent implantation alone (n = 10); baremetalstent implantation after pre-dilation with a drug-eluting balloon (n = 10); or bare-metalstent implantation followed by post-dilation with a drug-eluting balloon (n = 10). Six-monthfollow-up coronary angiography with optical coherence tomography imaging of the stentedsegment will be performed in all patients. Blood samples for the assessment of endothelialprogenitors cell levels will be collected on admission and at 6 months.DiscussionExperimental and early clinical data showed that inhibition of neointimal hyperplasia may beobtained by local administration of antiproliferative drugs loaded on the surface ofangioplasty balloons. The INtimal hyPerplasia evAluated by oCT in de novo COROnarylesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO) trial wasconceived to test the superiority of a strategy of bare-metal stent implantation with additionaldrug-eluting balloon use (either before or after stenting) versus a strategy of bare-metal stentimplantation alone for the reduction of neointimal hyperplasia. We also planned an ancillarystudy to assess the role of endothelial progenitors cells in the pathophysiology of neointimalhyperplasia.Trial registrationClinicaltrials.gov NCT01057563.

Open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery ERAS(R) programme (ORANGE II - Trial): study protocol for a randomized controlled trial

Ronald van Dam — 2012-05-06T00:00:00Z

Background: The use of laparoscopic liver resection and an enhanced recovery after surgery (ERAS(R))programme has been introduced to optimise postoperative recovery in liver surgery. Theadded value of laparoscopic surgery compared with open left lateral liver sectionectomywithin an ERAS programme in terms of time to functional recovery, length of hospital stay(LOS), long-term abdominal wall hernias, costs and quality of life (QOL) has never beenstudied in a randomised controlled trial. Therefore, this is the subject of the internationalmulticentre randomised controlled ORANGE II trial. Methods: Patients eligible for left lateral sectionectomy (LLS) of the liver will be recruited andrandomised at the outpatient clinic. All randomised patients will undergo surgery in thesetting of an ERAS programme. The experimental design produces two randomised arms(open and laparoscopic LLS) and a prospective registry. The prospective registry will bebased on patients that cannot be randomised because of the explicit treatment preference ofthe patient or surgeon, or because of ineligibility (not meeting the in- and exclusion criteria)for randomisation in this trial. Therefore, all non-randomised patients undergoing LLS will beapproached to participate in the prospective registry, thereby allowing acquisition of anuninterrupted prospective series of patients. The primary endpoint of the ORANGE II trial istime to functional recovery. Secondary endpoints are postoperative LOS, percentagereadmission, (liver-specific) morbidity, QOL, body image and cosmetic result, hospital andsocietal costs over 1 year, and long-term incidence of incisional hernias. It will be assumedthat in patients undergoing laparoscopic LLS, length of hospital stay can be reduced by 2days. A sample size of 55 patients in each randomisation arm has been calculated to detect a2 day reduction in LOS (90% power and alpha = 0.05 (two-tailed)).The ORANGE II trial is a multicenter randomised controlled trial that will provide evidenceon the merits of laparoscopic surgery in patients undergoing LLS within an enhancedrecovery ERAS programmeTrial registrationClinicalTrials.gov NCT00874224.

Impact assessment of the European Clinical Trials Directive: a longitudinal, prospective, observational study analyzing patterns and trends in clinical drug trial applications submitted since 2001 to regulatory agencies in six EU countries

Markus Hartmann — 2012-04-29T00:00:00Z

Background: Shifts in clinical trial application rates over time indicate if the attractiveness of a country or region for the conduct of clinical trials is growing or decreasing. The purpose of this observational study was to track changes in drug trial application patterns across several EU countries in order to analyze the medium-term impact of the EU Clinical Trials Directive 2001/20/EC on the conduct of drug trials. Methods: Rates of Clinical Trial Applications (CTA) for studies with medicinal products in those six countries in the EU, which authorize on average more than 500 trials per year, were analyzed. Publicly available figures on the number of annually submitted CTA, the distribution of trials per phase and the type of sponsorship were tracked; missing data were provided by national drug agencies. Results: Since 2001, the number of CTA in Italy and Spain increased significantly (5.0 and 2.5% average annual growth). For Italy, the gain was driven by a strong increase of applications from academic trial sponsors; Spain's growth was due to a rise in trials run by commercial sponsors. The Netherlands, Germany, France and the UK saw a decline (1.9, 2.3, 3.0 and 5.3% average annual diminution; significant (P < 0.05) except for Germany) in clinical drug trials. The decrease in the UK was caused by a sharp fall in academic trial activities. Across the six analyzed countries, no EU-wide trial-phase-specific patterns or trends were observed. Conclusions: The EU Clinical Trials Directive 2001/20/EC did not achieve the harmonization of clinical trial requirements across Europe. Rather, it resulted in the leveling of clinical trial activities caused by a continuing decrease in CTA rates in the Netherlands, Germany, France and the UK. Southern European countries, Italy and Spain, benefited to some extent from policy changes introduced by the Directive. In Italy's case, national funding measures helped to considerably promote the conduct of non-commercial trials. On the other hand, the EU Directive-driven transition from liberal policy environments, based on non-explicit trial approval through notifications, towards red-taped processes of trial authorization, contributed to the decreases in trial numbers in Germany and the UK. In the latter case, national research governance concerns had a share in the country's marked decline. However, different EU member states successfully developed best practices, which a new European legislation should take into consideration to resume Europe's attractiveness and international competitiveness for the conduct of clinical trials.

Assessing the effectiveness of 'pulse radiofrequency treatment of dorsal root ganglion' in patients with chronic lumbar radicular pain: study protocol for a randomized control trial

Harsha Shanthanna — 2012-04-28T00:00:00Z

Background: Chronic lumbar radicular pain can be described as neuropathic pain along the distribution of a particular nerve root. The dorsal root ganglion has been implicated in its pathogenesis by giving rise to abnormal impulse generation as a result of irritation, direct compression and sensitization. Chronic lumbar radicular pain is commonly treated with medications, physiotherapy and epidural steroid injections. Epidural steroid injections are associated with several common and rarer side effects such as spinal cord infarction and death. It is essential and advantageous to look for alternate interventions which could be effective with fewer side effects.Pulse radio frequency is a relatively new technique and is less destructive then conventional radiofrequency. Safety and effectiveness of pulse radio frequency in neuropathic pain has been demonstrated in animal and humans studies. Although its effects on dorsal root ganglion have been studied in animals there is only one randomized control trial in literature demonstrating its effectiveness in cervical radicular pain and none in lumbar radicular pain. Our primary objective is to study the feasibility of a larger trial in terms of recruitment and methodology. Secondary objectives are to compare the treatment effects and side effects.Methods/designsThis is a single-center, parallel, placebo-controlled, triple-blinded (patients, care-givers, and outcome assessors), randomized control trial. Participants will have a history of chronic lumbar radicular pain for at least 4 months in duration. Once randomized, all patients will have an intervention involving fluoroscopy guided needle placement to appropriate dorsal root ganglion. After test stimulation in both groups; the study group will have a pulse radio frequency treatment at 42degreesC for 120 s to the dorsal root ganglion, with the control group having only low intensity test stimulation for the same duration. Primary outcome is to recruit at least four patients every month with 80% of eligible patients being recruited. Secondary outcomes would be to assess success of intervention through change in the visual analogue scale measured at 4 weeks post intervention and side effects. Allocation to each group will be a 1:1 ratio with allocation block sizes of 2, 4, and 6.Trial registrationClinicalTrials.gov NCT01117870

UK Dermatology Clinical Trials Network's STOP GAP Trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

Fiona Craig — 2012-04-28T00:00:00Z

Background: Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. Methods: The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial.Trial registrationCurrent controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

The value of the pragmatic-explanatory continuum indicator summary wheel in an ongoing study: the bullous pemphigoid steroids and tetracyclines study

Daniel Bratton — 2012-04-27T00:00:00Z

Background: The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool is intended to be used in the design phase of trials to help investigative teams design trials in-line with their purpose. Our team applied this tool to an ongoing trial (BLISTER) to determine whether the initial suggestion among some team members that the trial could be described as largely pragmatic was the consensus. Methods: Each of the six members of the BLISTER trial team was sent a blank PRECIS wheel to independently complete. The results obtained were averaged and plotted on a single PRECIS wheel to illustrate the degree of pragmatism of the trial. Results: The trial team found that the design of the trial was closest to the pragmatic end of the pragmatic-explanatory continuum. The strongest consensus was found on the 'flexibility of the comparison intervention' and 'practitioner adherence' domains (SD = 13). The trial team appeared to disagree most on the 'eligibility criteria' (SD = 35) and 'participant compliance' (SD = 31) domains, although the large standard deviations were a result of a single outlier in the two domains. Conclusion: The PRECIS tool can be used to retrospectively determine the pragmatism of a trial provided enough expertise and information on the trial is available. Illustrating the design of a trial on the PRECIS wheel can help research users more easily identify studies of interest. We hope our recommendations for applying this useful tool will encourage others to consider using it when designing, conducting and reporting studies.Trial registrationCurrent Controlled Trials ISRCTN13704604

Alcohol email assessment and feedback study dismantling effectiveness for university students (AMADEUS-1): study protocol for a randomized controlled trial

Jim McCambridge — 2012-04-27T00:00:00Z

Background: Alcohol causes huge problems for population health and for society, which require interventions with individuals as well as populations to prevent and reduce harms. Brief interventions can be effective and increasingly take advantage of the internet to reach high-risk groups such as students. The research literature on the effectiveness of online interventions is developing rapidly and is confronted by methodological challenges common to other areas of e-health including attrition and assessment reactivity and in the design of control conditions. Methods: The study aim is to evaluate the effectiveness of a brief online intervention, employing a randomized controlled trial (RCT) design that takes account of baseline assessment reactivity, and other possible effects of the research process. Outcomes will be evaluated after 3 months both among student populations as a whole including for a randomized no contact control group and among those who are risky drinkers randomized to brief assessment and feedback (routine practice) or to brief assessment only. A three-arm parallel groups trial will also allow exploration of the magnitude of the feedback and assessment component effects. The trial will be undertaken simultaneously in 2 universities randomizing approximately 15,300 students who will all be blinded to trial participation. All participants will be offered routine practice intervention at the end of the study.DiscussionThis trial informs the development of routine service delivery in Swedish universities and more broadly contributes a new approach to the study of the effectiveness of online interventions in student populations, with relevance to behaviors other than alcohol consumption. The use of blinding and deception in this study raise ethical issues that warrant further attention.Trial registrationISRCTN28328154

Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial

Sulman Rafiq — 2012-04-27T00:00:00Z

Background: Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively. Methods: This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery. Conclusions: The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy.Trial registrationClinicaltrials.gov Identifier NCT01046942