Please select the eligibility criteria that correspond to the clinical trial below.
Title: Double Blind Randomized Controlled Trial of Recombinant Human Platelet Derived Growth Factor-BB Gel (Regranex Gel®) Versus Hydrogel (Duoderm Hydrogel®) for Healing of MARTORELL's Hypertensive Leg Ulcers. ERAN Trial.
Brief Summary: Background: No medical treatment has proved its efficacy for the treatment of hypertensive leg ulcers in a well designed trial.

Primary aim of the study: to compare the rate of healing in hypertensive leg ulcers treated with becaplermin gel (Regranex Gel®) daily application versus the application of the same quantity of an hydrogel (Duoderm Hydrogel™), corresponding to the excipient of becaplermin gel.

Method: Ambulatory or hospitalized patients presenting with an hypertensive leg ulcer, were randomized to receive either a daily application of becaplermin gel or hydrogel during 8 weeks. At week 8, a pinch graft was proposed to patients whom the ulcer has not healed.

Primary aim of the study: Complete closure at week 8

Secondary aims: percentage of wound area reduction at week 8, complete closure at week 12, pain and quality of life during treatment

Study hypothesis: becaplermin gel may promote the healing of hypertensive leg ulcers and be an alternative medical treatment to the skin graft usually proposed


Options:
A: Inclusion Criteria:

* Provide informed consent.
* Age ≥ 18 years and of either sex.
* Willing to comply with protocol instructions, including allowing all study assessments.
* Have a venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus), with a surface area ≥ 2.0 cm2 and ≤ 12.0 cm2
* Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.
* Arterial supply adequacy confirmed
* Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon, muscle, or bone.
* Target ulcer duration ≥ 6 weeks but ≤ 104 weeks (24 months).
* Acceptable state of health and nutrition

Exclusion Criteria:

* History of anaphylaxis, serum sickness, or erythema multiforme reaction to aprotinin, bovine serum albumin or bovine serum proteins, penicillin, streptomycin, amphotericin B.
* Prior diagnosis of Systemic Lupus Erythematosus with elevated anti-DNA antibody titers, Buerger's disease (thromboangiitis obliterans), current diagnosis of vasculitis, or current diagnosis of claudication.
* Therapy with another investigational agent within thirty (30) days of Screening, or during the study.
* A target ulcer of non-venous etiologies (e.g., sickle cell anemia, necrobiosis lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic).
* Documented history of osteomyelitis at the target wound location within 6 months preceding the Screening Visit.
* Refusal of or inability to tolerate compression therapy.
* Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit.
* History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix or adequately treated non-melanoma skin cancers).
* Any prior exposure to HP802-247 or its vehicle.
B: Inclusion Criteria:

* Provide informed consent.
* Age ≥ 18 years and of either sex.
* Willing to comply with protocol instructions, including allowing all study assessments.
* Have a venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus), with a surface area \>12 cm2 to ≤ 36 cm2
* Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.
* Arterial supply adequacy confirmed
* Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon, muscle, or bone.
* Target ulcer duration ≥ 6 weeks but ≤ 104 weeks (24 months).
* Acceptable state of health and nutrition

Exclusion Criteria:

* History of anaphylaxis, serum sickness, or erythema multiforme reaction to aprotinin, bovine serum albumin or bovine serum proteins, penicillin, streptomycin, amphotericin B.
* Prior diagnosis of Systemic Lupus Erythematosus with elevated anti-DNA antibody titers, Buerger's disease (thromboangiitis obliterans), current diagnosis of vasculitis, or current diagnosis of claudication.
* Therapy with another investigational agent within thirty (30) days of Screening, or during the study.
* A target ulcer of non-venous etiologies (e.g., sickle cell anemia, necrobiosis lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic).
* Documented history of osteomyelitis at the target wound location within 6 months preceding the Screening Visit.
* Refusal of or inability to tolerate compression therapy.
* Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit.
* History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix or adequately treated non-melanoma skin cancers).
* Any prior exposure to HP802-247 or its vehicle.
C: Inclusion Criteria:

* Provide informed consent.
* Willing to comply with protocol instructions, including allowing all study assessments.
* Have a venous leg ulcer (venous etiology)between the knee and ankle, at or above the malleolus.
* Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.
* Target ulcer duration greater than or equal to 6 weeks but less than or equal to 24 months.

Exclusion Criteria:

* Women who are pregnant or lactating
* Therapy with another investigational agent within thirty (30) days of Screening, or during the study.
* A target ulcer of non-venous etiologies.
* Refusal of or inability to tolerate compression therapy.
* Therapy of the target ulcer with tissue-engineered cell-based skin equivalents within 30 days preceding the Screening Visit.
* Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit.
D: Inclusion Criteria:

* patients 18 years of age or older, able to give informed consent and to follow the treatment procedure
* target ulcer area between 1 and 30 cm2
* consecutive patients presenting with one or more leg ulcers diagnosed as hypertensive MARTORELL's ulcers
* presence of an arterial hypertension, according to the WHO criteria, treated or not; and/or presence of a diabetes treated by oral agent, insulin or diet
* absence of clinical signs of chronic venous insufficiency: skin hyperpigmentation, lipodermatosclerosis
* absence of significant peripheral arterial occlusive disease: presence of peripheral pulses or ankle brachial index ≥0.8
* absence of clinical sign of arterial insufficiency: intermittent claudication, resting pain
* superficial spreading necrotic ulcer
* presence of spontaneous pain
* presence of a red purpuric margin

Exclusion Criteria:

* pregnancy
* allergy to hydrogel or to becaplermin gel
* uncontrolled or evolving systemic disease: cardiac or renal failure, hepatic insufficiency, malignant disease, thrombotic disease, vasculitis or other connective tissue disorder
* presence of a cryoglobulinemia
* serum creatinine concentration greater than 200µmol/L or uncontrolled diabetes (fasting blood glucose \> 2,5 g/L under treatment)
* concomitant treatment by ILOMEDINE
* bone, joint or tendon (except for achilles tendon) exposition in the wound
* systemic treatment with corticosteroid agents or cytotoxic drugs in the past 3 months before inclusion

Answer: D