E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047013 |
E.1.2 | Term | Varicose veins of lower extremities |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the clinical and cost-effectiveness of conventional surgery with two minimally invasive treatment modalities (a) foam sclerotherapy alone of main long or short saphenous trunk and non-trunk varicosities and (b) Endovenous laser ablation (EVLA) of main trunk including foam sclerotherapy of non-trunk varicosities, if required, performed under local anaesthetic in respect of quality of life for each intervention at 6 months (and ultimately through to 5 years) and cost-effectiveness as cost per quality adjusted life year (QALY) gained |
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E.2.2 | Secondary objectives of the trial |
To compare the two novel interventions against conventional surgery in respect of: (i) Clinical success as determined by residual varicose veins, complication rates and return to normal activities. (ii) Technical success (duplex scan verified partial or complete ablation of, or the presence of reflux in, the main long or short saphenous trunk veins) at 6 months (and ultimately through to 5 years). In addition, any development of deep venous incompetence and neovascularisation up to 5 years. (iii) Cost to the health service and patients of each intervention and any subsequent care.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study 1 - Exeter Duplex sub-study (version 1, March 2009) This is a non-interventional sub-study (ie it does not involve any change to the IMP delivered as part of the CLASS trial). The sub-study will be carried out in one site only. The objectives are (i) to link patients' experiences of varicose vein symtoms with their varicose vein geograph and (ii) to establish, in patients treated with foam sclerotherapy, whether there is any relationship between the patients' view of the outcome of treatment and the duplex ultrasound haemodynamic evidence gathered post-procedure. No additional data is collected as part of this sub-study. However patients are required to give additional consent for their data to be used for this sub-study. The CLASS trial protocol does not change in light of this sub-study. A protocol for the sub-study has been developed and is enclosed.
Sub-study 2 - VVaT sub-study (version 1, March 2009) This is a non-interventional sub-study (ie it does not involve any change to the IMP delivered as part of the CLASS trial). The sub-study will be carried out in one site only. The aim of the sub-study is to evaluate the quality of the leaflet (Varicose Veins and Treatment) as an information tool from a patient perspective. We propose to interview four patients who have agreed to take part in the CLASS study to find out their views on the leaflet in terms of how readable they found it. Patients will be given information about this interview based sub-study, and if they consent to take part, they will be asked to sign a consent form for this sub-study. The CLASS trial protocol does not change in light of this sub-study. A protocol for the sub-study has been developed and is enclosed.
Sub-study 3 - A qualitative study to explore patient preferences about recruitment into the CLASS trial (version 1, March 2010) This is a non-interventional sub-study (ie it does not involve any change ot the IMP delivered as part of the CLASS trial). The sub-study will be carried out in one site only (Exeter). The aim is to integrate qualitative research methods into the recruitment processes to (i) understand information provision in consultations and (ii) explore participants’ views of the process to establish whether it is possible to improve these and increase trial recruitment. Patients potentially eligible for the CLASS trial will also be invited to participate in this sub-study. Consultations between consenting patients and consultant surgeons will be audio-recorded. Patients will be interviewed following consultations to understand their interpretation of the information provision and to explore their understanding of randomisation. Patients will be given information about this sub-study, and if they consent to take part, they will be asked to sign a consent form for one or both of the phases (audtio-recording/interview). The CLASS trial protocol does not change in light of this sub-study. A protocol for the sub-study has been developed and is enclosed, together with supporting documentation. |
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E.3 | Principal inclusion criteria |
Adult patients (aged over 18 years old) who are referred to the surgical out-patient department for treatment of primary varicose veins with symptomatic (CEAP grade 2 or above) primary long or short saphenous main stem incompetence (reflux >1 second on duplex scanning) are eligible for inclusion. |
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E.4 | Principal exclusion criteria |
Current deep vein thrombosis, acute superficial vein thrombosis, allergy to sclerosant, pregnancy or breast feeding, history of hypercoagulability, arterial disease (ankle brachial pressure index <0.8), inability to mobilise post-procedure, needle phobia, long or short saphenous vein less than 3mm in diameter or greater than 15mm and tortuous veins that are considered to be unsuitable for EVLA due to difficulties in passing the guide wire, inability to provide informed consent, inability to complete study questionnaires.
Other exclusion criteria include those specifically mentioned on the fibro-vein (sodium tetradecyl sulphate) prescribing information leaflet which are: varicosities caused by pelvic or abdominal tumours, cardiac failure, pulmonary oedema, local or systemic infection.
All varicose vein treatment should be used with care in patients taking oral contraceptives or hormonal replacement therapy. The treating surgeon will either ask the patient to discontinue the oral contraceptive or hormonal replacement therapy prior to treatment or will prescribe heparin prophylaxis therapy.
Patients who are not fit for a general anaesthetic due to significant systemic disease, morbid obesity or other causes will be excluded from the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
We will assess outcomes up to 6 months, but with possible long-term follow-up to 5 years through a separate funding application. 1. Primary patient outcome: Disease specific (Aberdeen Varicose Vein Questionnaire) and generic quality of life (EQ-5D, SF-36) at 6 months 2. Primary economic outcome: Incremental cost per quality adjusted life years (QALY) at 6 months
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
(i) conventional surgery; (ii) endovenous laser ablation with foam sclerotherapy if required |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of clinical follow-up is the 6 month visit (last visit) of last subject recruited. The end of study is defined as the end of funding. The data monitioring committee will decide on any stop criteria other than completion of the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |