E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Varicose veins (VVs) or Superficial Venous Insufficiency (SVI) of the legs results from inflammation mediated damage to vein structure, allowing reverse flow. SVI affects 30% of adults and is associated with symptoms causing pain and disability; furthermore 3-10% have soft tissue damage and 1-2% suffer with venous ulcer disease. |
|
E.1.1.1 | Medical condition in easily understood language |
Valves within leg veins let blood through towards the body and heart. If they stop working properly, the leaking valves cause vein to become swollen and enlarged called "varicose veins". |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
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 |
Randomised trials have established that closing veins using a heat source such as laser has significantly higher success rates than using chemicals, however heat treatment requires multiple additional uncomfortable injections of local anaesthetic. Recently a newer treatment mechanochemical ablation (MOCA) has been developed aiming to provide improved success rates similar to those seen with heat treatment, yet still avoid additional injections. This technology involves a spinning wire inside the vein which releases the chemical. The wire performs several actions which makes the vein more susceptible to the action of the chemical.
Early non-randomised data suggests that MOCA may have similar success rates as heat, which seems very promising and this trial aims to randomly allocate patients to receive treatment with MOCA or with a popular heat method endovenous laser ablation (EVLA). The results can then be directly compared to see whether there are any differences in efficacy, ef |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 18 or over - Symptomatic SVI which will likely benefit from treatment in the opinion of an experienced specialist and the participant - Clinical grades C2-C6 on the CEAP system - Superficial axial incompetence with proposed treatment lengths of at least 10cm - Treatment with either endovenous laser ablation or mechanochemical ablation is technically feasible in the view of an experienced endovenous specialist - Patient is willing to participate (including acceptance of randomisation to either treatment) and give valid, informed consent in the English language |
|
E.4 | Principal exclusion criteria |
- One of the treatments is thought to be preferable by either the patient or an experienced endovenous specialist - Unwilling or inability to comply with the requirements for follow-up visits - Known allergy to any medications used during treatment - Known right to left circulatory shunt - Evidence of acute deep venous thrombosis or complete ipsilateral occlusion - Pelvic vein insufficiency - Active or recent thrombophlebitis (within 6 weeks) - Impalpable foot pulses with Ankle-Brachial Pressure Index of less than 0.8 - Pregnancy or breast feeding - Active malignancy - Immobility - Have been included in other CTIMP trials within the last 6 months |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The joint primary outcomes will assess the hypothesised advantaged and disadvantages of mechanochemical ablation (MOCA) when compared with endovenous laser ablation (EVLA), the current first choice treatment of superficial venous insufficiency (SVI).
The first will be patient reported intra-procedural pain measured on a standardised visual analogue scale (VAS).
The second will be technical efficacy at 1 year, with successful procedure defined as complete occlusion of the target vein segment. This will be assessed during duplex ultrasound. Recanalisation at 1 year is defined as blood flow within the target vein that had been treated. This is broken down into partial <25% or full ≥25% of the length of the treated vein. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will record their intra- and post-procedural pain on visual analogue scale (VAS). They will complete this immediately following axial treatment and again following tributary treatment. They will then go on to record this in a diary, providing a daily score for the first week.
The type and daily dosage of any analgesia taken by patients will also be recorded in the diary for the first week by the patient.
Patients will be followed up at 1 week, 6 weeks, 6 months and 1 year, during which they will be assessed with duplex ultrasound to determine the technical efficacy of the treatments. |
|
E.5.2 | Secondary end point(s) |
- Disease specific quality of life using the Aberdeen Varicose Vein Questionnaire (AVVQ), the Chronic Venous Insufficiency Questionnaire (CIVIQ), and the VEnous INsufficiency Epidemiological and Economic Study to evaluate Quality of Life and Symptoms (VEINES-QOL/Sym). - Generic quality of life using the Short Form 36 (SF-36), EuroQol (EQ5D), and SF6D. - Bruising visual analogue scale on a 100mm unmarked scale. - Satisfaction visual analogue scale on a 100mm unmarked scale. - Cosmesis visual analogue scale on a 100mm unmarked scale. - Recovery time in terms of time taken to return to work and normal activities. - Clinical severity using the CEAP (Clinical severity, Etiology, Anatomy and Pathophysiology) classification, and Venous Clinical Severity Score (VCSS). - Complications - Surface planimetry of skin changes and complications estimated by measurement of tracing on acetate pre-printed with 1cm2 grids. - Duplex ultrasound to assess treatment efficacy. - Costs and resource use. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients will be followed up at 1 week, 6 weeks, 6 months and 1 year, during which they will be assessed for the secondary outcome measures. |
|
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 | Yes |
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 |
Endovenous laser ablation (EVLA) |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of trial is defined as the Last Visit of the Last Subject (LVLS) completing their 1 year follow-up assessment. Participants may be contacted and invited for further follow-up at 5 and 10 years, in order to assess the long-term effects of intervention, and these attendances are voluntary. Hospital records will be checked beforehand to establish the patient status and contact details. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |