PROSPERO International prospective register of systematic reviews Drug-eluting balloon angioplasty versus non-stenting balloon angioplasty for peripheral arterial disease of the lower limbs [Cochrane Protocol] Ahmed Kayssi, Talal Al-Atassi, George Oreopoulos, Graham Roche-Nagle, Kong Teng Tan, Dheeraj Rajan Citation Ahmed Kayssi, Talal Al-Atassi, George Oreopoulos, Graham Roche-Nagle, Kong Teng Tan, Dheeraj Rajan. Drugeluting balloon angioplasty versus non-stenting balloon angioplasty for peripheral arterial disease of the lower limbs [Cochrane Protocol]. PROSPERO 2015:CRD42015020466 Available from http://www.crd.york.ac.uk/prospero_rebranding/display_record.asp?id=crd42015020466 Review question(s) To assess the efficacy of drug-eluting balloons (DEBs) compared with non-stenting balloon angioplasty in patients with symptomatic lower-limb peripheral arterial disease (PAD). Searches All references to appendices are to those in the full protocol on the Cochrane Library. Electronic searches The Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator (TSC) will search the Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library (www.thecochranelibrary.com). See Appendix 1 for details of the search strategy which will be used to search CENTRAL. The Specialised Register is maintained by the TSC and is constructed from weekly electronic searches of MEDLINE, EMBASE, CINAHL, AMED, and through handsearching relevant journals. The full list of the databases, journals and conference proceedings which have been searched, as well as the search strategies used, are described in the Specalised Register section of the Cochrane Peripheral Vascular Diseases Group module in The Cochrane Library (www.thecochranelibrary.com). In addition, the TSC will search the following trial databases for details of ongoing and unpublished studies. World Health Organization International Clinical Trials Registry http://apps.who.int/trialsearch/ ClinicalTrials.gov http://clinicaltrials.gov/ Current Controlled Trials http://www.controlled-trials.com/ Nederlands Trials Register http://www.trialregister.nl/trialreg/admin/rctsearch.asp Searching other resources We will examine the bibliographies of relevant papers found from the electronic searches to identify other studies. If we identify ongoing studies or studies that have been completed but not published, we will then contact the study authors or device manufacturers to attempt to obtain the study data. Types of study to be included Randomized-controlled trials that compare drug-eluting balloons (DEBs) with non-stenting balloon angioplasty for intermittent claudication (IC) or critical limb ischemia (CLI). Condition or domain being studied The Cochrane Peripheral Vascular Diseases Group Page: 1 / 5
Participants/ population Patients with IC or CLI undergoing drug-eluting or uncoated balloon angioplasty for symptomatic lower-limb PAD. We plan to present the data by the severity of disease when IC and CLI patient characteristics are reported. If data of the included studies are not presented by these groups then we will present combined data. Intervention(s), exposure(s) We will compare DEBs for PAD of the lower limbs with uncoated balloon angioplasty. Endovascular access in the included studies must have been established percutaneously or through a limited incision. We will include studies of DEBs for the treatment of in-stent restenosis of the lower-limb. We will exclude studies where DEBs were used simultaneously in combination with other angioplasty techniques (such as hybrid procedures involving surgery and DEBs). The review will focus on primary arterial interventions only. We will exclude reinterventions and studies using cutting balloon angioplasty. Comparator(s)/ control Uncoated balloon angioplasty. Outcome(s) Primary outcomes Amputation-free survival, defined as the probability of being alive without an amputation Amputation-free rate Vessel patency (primary and secondary), as determined by delayed arterial lumen loss, target lesion revascularization, and restenosis rate measured with duplex ultrasound or angiography Death Secondary outcomes Change in Fontaine's stage or Rutherford category of PAD (Norgren 2007) Improvement in ankle brachial index (ABI) Change in quality of life (QoL) scores Change in treadmill walking distance Data extraction, (selection and coding) Selection of studies Two authors (AK and TA) will independently select trials for inclusion in this review. These trials will be sent to a third author (DR), who will assess and confirm their suitability for inclusion and act as an adjudicator in the event of disagreement. The above section Criteria for considering studies for this review details the inclusion criteria used in this selection process. We will present a flow diagram of our selection of studies. Data extraction and management Two authors (AK and TA) will extract the data from each trial, including patient demographics (age, gender, comorbidities, Fontaine s stage or Rutherford category of PAD, and ABI), interventions (DEBs and other balloon types, vessels treated, history of previous stent placement), and outcomes (as specified in the section Criteria for considering studies for this review). A third author (DR), will then cross-check the data; this same author will also act as an adjudicator in the event of disagreement. Statistical analysis will comply with the standard methods of the Cochrane PVD Group. We will use the computer software package Review Manager (RevMan 2014) to perform all statistical analyses and generate figures. Risk of bias (quality) assessment Assessment of risk bias in included studies Two authors (AK and TA) will assess potential risks of bias for all included studies using the Cochrane Collaboration's tool for assessing risk of bias (Higgins 2011). The tool assesses bias in six different domains: sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, incomplete outcome data, selective Page: 2 / 5
outcome reporting, and other sources of bias. Each domain will receive a score of high, low, or unclear depending on each review author's judgement. A third author (DR) will act as an adjudicator in the event of disagreement. Where doubt exists as to a potential risk of bias, we will contact the study authors for clarification. Strategy for data synthesis Data synthesis We will use a fixed-effect model to calculate the pooled treatment effect data and 95% (CIs) for continuous and binary outcome variables, as detailed above. We will use the random-effects model in the event that significant heterogeneity (defined as I 2 greater than 75%) is observed. We will create a forest plot for each treatment effect, as per Cochrane PVD Group guidelines. Assessment of heterogeneity We will assess inter-study heterogeneity visually using a forest plot. We will also calculate the I 2 statistic to measure the amount of inter-study heterogeneity. We will consider I 2 values less than 50% as indicative of low heterogeneity, I 2 values between 50% and 75% as indicative of moderate heterogeneity, and I 2 values greater than 75% as indicative of significant heterogeneity (Higgins 2011). Assessment of reporting biases If sufficient studies are available (> 10 studies) (Higgins 2011) we will construct a funnel plot using the included studies to assess publication bias. Sensitivity analysis We will sequentially exclude studies with a high risk of bias in several domains (as described in the section Assessment of risk of bias in included studies) and we will again perform a pooled analysis to conduct a sensitivity analysis. We will do this to assess whether the inclusion of studies, deemed to be biased, impacts the final analysis. Analysis of subgroups or subsets We will perform subgroup analyses by type of DEB pharmacological agent, the arterial segments treated, and the severity of PAD, if data are available. Dissemination plans This is a Cochrane review and will be published in full online in the Cochrane Database of Systematic Reviews (CDSR), which is a core component of The Cochrane Library. Contact details for further information Ahmed Kayssi ahmed.kayssi@mail.utoronto.ca Organisational affiliation of the review The Cochrane Collaboration http://www.cochrane.org/ Review team Dr Ahmed Kayssi, University of Toronto Dr Talal Al-Atassi, University of Ottawa Heart Institute George Oreopoulos, University of Toronto Dr Graham Roche-Nagle, University of Toronto Dr Kong Teng Tan, University of Toronto Dr Dheeraj Rajan, University of Toronto Anticipated or actual start date 15 September 2014 Page: 3 / 5
Anticipated completion date 15 September 2016 Funding sources/sponsors None specified Conflicts of interest AK: none known TA: none known GO: none known GR: reports having received consultancy fees from Cordis Medical and Cook Medical related to giving lectures/proctoring on AAA and PVD with no exclusive relationship to promote their products KT: Our site is involved in many multicenter clinical trials. The funds (Biotronic Inc., Medtronic Endovascular) are managed independently by the department research board. We also received funding for teaching and research activities from the industry (Cook Medical, Covidien, Gore Medical) and again it is managed by the research department. I do receive direct payment from Cook Medical and Cordis Medical for proctoring and teaching advance aortic aneurysm stent graft. DR: reports having received consultancy fees from TVA Medical (no commercial products, start up company for percutaneous creation of dialysis fistulas) and Cordis Medical (provision of services for lectures around AAA and peripheral vascular disease with no requirement to endorse Cordis products) Other registration details This is a protocol for a Cochrane review, full details are available on The Cochrane Library. Language English Country Canada Subject index terms status Subject indexing assigned by CRD Subject index terms Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Humans; Lower Extremity; Peripheral Arterial Disease; Peripheral Vascular Diseases; Stents Stage of review Ongoing Date of registration in PROSPERO 19 May 2015 Date of publication of this revision 19 May 2015 DOI 10.15124/CRD42015020466 Page: 4 / 5
Powered by TCPDF (www.tcpdf.org) Stage of review at time of this submission Started Completed Preliminary searches Yes Yes Piloting of the study selection process Yes No Formal screening of search results against eligibility criteria No No Data extraction No No Risk of bias (quality) assessment No No Data analysis No No PROSPERO International prospective register of systematic reviews The information in this record has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Page: 5 / 5