PICO Venous Leg Ulcers (VLU) Reimbursement Study

This study intends to demonstrate the superiority of PICO treatment when applied up to 12 weeks, versus Standard of Care (SOC) in the treatment of hard to heal Venous Leg Ulcers (VLU) by community-based practitioners. The primary endpoint is the incidence of confirmed healed VLUs at 12 weeks or before, in the PICO treatment group versus the SOC group. The study hypothesis is based on the Kirsner study (Kirsner R, Dove C, Reyzelman A, Vayser D, Jaimes H. A prospective, randomized, controlled clinical trial on the efficacy of a single-use negative pressure wound therapy system, compared to traditional negative pressure wound therapy in the treatment of chronic ulcers of the lower extremities. Wound Repair Regen. 2019 Sep;27(5):519-529)), which compared PICO treatment to traditional NPWT (t-NPWT); the ITT analysis in the subgroup of patients with VLU showed 45.1% wound closure (confirmed wound healing) at 12 weeks in the PICO group as compared to 28% in the t-NPWT group, yielding a difference of 17.1%, 95% Confidence Interval = (-1.9%;+35.4%). For our study, the Sponsor made the assumptions that the t-NPWT healing proportion (28%) can be used as conservative estimate for the control group proportion and that the PICO group should provide at least a 17% improvement over standard of care. Adaptative design is chosen to adjust the sample size using the re-assessment size method to preserve alpha risk (α) level.

This is a national, multicentre, pragmatic, randomized, controlled superiority study in which PICO treatment with compression therapy will be compared against Standard of Care (i.e. traditional wound dressings with compression therapy). There will be two parallel treatment arms with a 1:1 allocation ratio and a stratification on wound duration and size. There will be an additional blind assessment for the primary outcome measure.

Approximately 37 investigational sites located in France will be enrolled. At each site, a community-based practitioner (general practitioner or specialist) will be enrolled as Principal Investigator (PI). District nurses will be responsible for providing wound care in homecare setting. Duly informed and eligible patients will complete an inclusion visit after which they will enter in a 2-week run-in period in which subjects will be treated with standard of care. After these 2 weeks of run-in, eligibility to randomization will be assessed using pre-specified criteria listed in the protocol, that aim to confirm that the wound does not respond to an adequately conducted standard of care in a satisfactory manner, including subject compliance with compression therapy.

Upon randomization, baseline data will be collected, and each subject will be followed-up by the PI for 12 weeks. The PI will conduct 3 visits, i.e., at Week 4 (D28±3 days), Week 8 (D56±3 days), and Week 12 (D84±3 days). Relevant study data will be collected at these visits. In the event wound healing is observed during the 12-week follow-up period of the study either by the PI or by the home care nurse, a Wound Healing Confirmation Visit needs to be conducted with the PI 2 weeks later (±3 days) to confirm that the wound is still healed. Only wounds still healed at the wound healing confirmation visit will be counted as "healed" in the primary endpoint analysis. This means that for wounds that are not healed by Week 12, the visit with the PI at Week 12 will be the final study visit for the subject. Following, because a Wound Healing Confirmation Visit needs to be conducted 2 weeks (±3 days) following the initial observation of wound healing, which can occur at any time throughout the 12 week follow-up period, the Wound Healing Confirmation Visit can occur at any time as well, but at the latest 2 weeks (±3 days) following the visit at Week 12, i.e. at week 14±3 days.

In between study visits with the PI, patients are cared for at home by their home care nurse who will also be trained on the study. The study nurse will be collecting study related data as well using a secure mobile application.

Eligibility Criteria:
Inclusion Criteria:

* Subject signed informed consent
* Both gender adult ≥ 18 years old
* Venous leg ulcer (VLU) diagnosed by:

  * ABPI ≥ 0.7 and \< 1.3 within the last 3 months
  * If ABPI \< 1.3, one of the following measures should be available:

    * Toe Brachial Pressure Index (TBPI) \> 0.7
    * Toe pressure (TP) \> 50 mmHg
    * Transcutaneous oxygen pressure (TcPO2) \> 30 mmHg
* VLU duration ≥ 6 weeks
* VLU surface area:

  * Isolated leg ulcer: ≤ 100 cm\^2
  * Non-isolated leg ulcers: pooled surface area ≤ 100 cm\^2 that can be covered by a single dressing
* Exuding VLU according to clinical judgement
* The subject is in acceptable state of health and nutrition according to clinical judgement
* The subject is able to follow the protocol instruction and willing to comply with compression therapy
* The subject is affiliated to a French Health insurance scheme

Exclusion Criteria:

* Clinical evidence of VLU infection \[i.e. presence of at least 3 overt signs of local infection (e.g., erythema, warmth, swelling, pain, odor) or signs of spreading or systemic infection)
* Wound with necrotic tissue after debridement
* Sloughy wound (100% of slough) after debridement
* Exposed arteries, veins, nerves or organs
* Current therapy with chronic oral corticosteroids (\>10 days)
* Previous therapy with negative pressure wound therapy device or hyperbaric oxygen within 7 days prior to enrolment
* Arterial insufficiency non-revascularized
* Wound actively bleeding
* Malignant wound
* Enrolled in another clinical trial or being in a period of exclusion from a previous clinical trial
* Person belonging to a population referred to in articles 64 (incapacitated subjects), 65 (minors), 66 (pregnant or breastfeeding women), 67 (persons performing mandatory military service, persons deprived of liberty, persons who, due to a judicial decision cannot take part in clinical investigations) and 68 (patients in emergency situation) of the Medical Device Regulation