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:

1. Participants with an ankle brachial index (ABI) ≤ 0.90 will be eligible for participation.
2. Participants with an ABI \> 0.90 but ≤ 1.00 who experience a 20% drop in ankle pressure after the heel-rise exercise will be eligible.
3. Participants with an ABI \> 0.90 who have medical record evidence of prior lower extremity revascularization and experience a 20% drop in ankle pressure after the heel-rise exercise will be eligible for inclusion.
4. Participants with an ABI \> 0.90 who have medical record evidence of a non-invasive vascular laboratory test result consistent with PAD. Note that a screen-positive test from Lifeline Screening is not sufficient for inclusion in the study.

Exclusion Criteria:

The following exclusion criteria will be initially assessed by telephone:

1. Below or above-knee amputation.
2. Wheelchair confinement.
3. Use of a walking aid other than a cane (i.e. people using walkers).
4. Non-English speaking.
5. Significant hearing impairment.
6. Significant visual impairment.
7. Diagnosis of Parkinson's disease.
8. Inability to return to the medical center at the required visit frequency (three times per week).
9. \> Class II New York Heart Association heart failure or angina (symptoms at rest or with minimal exertion).
10. Any increase in angina pectoris symptoms during the previous 6 months or angina at rest.
11. Foot ulcer. (Participants with a foot ulcer will be excluded by telephone and/or during a baseline study visit).
12. Lower extremity revascularization in the last three months or major orthopedic surgery during the previous three months.
13. Myocardial infarction, stroke, or coronary artery bypass grafting during the previous 3 months.
14. Major medical illnesses including end stage renal disease requiring dialysis and chronic lung disease requiring oxygen, since these individuals may not be able to adhere to study requirements. Participants who only use oxygen at night may still qualify.
15. Potential participants who have received G-CSF, GM-CSF, or erythropoietin within the past year will be excluded because these interventions may influence study outcomes independently of the interventions.
16. Pre-menopausal women will be excluded because cyclic estrogen changes can influence progenitor cell levels.
17. Potential participants with diabetes and documented proliferative retinopathy will be excluded because GM-CSF may exacerbate this condition.
18. Potential participants with a history of myeloid malignancy will be excluded because GM-CSF may exacerbate these conditions.
19. Potential participants who have been treated for late stage cancer during the past three years, since GM-CSF may theoretically activate quiescent cancer cells.
20. Planned lower extremity revascularization within the next 6 months.
21. Current participation in another clinical trial. If a participant recently completed a clinical trial, at least three months must have passed before they can be considered for the PROPEL Trial. However, for a clinical trial of stem cell or gene therapy intervention, potential participants will be potentially eligible immediately after the final study visit of the stem cell or gene therapy clinical trial, so long as at least six months has passed since the participant received their final treatment in the stem cell or gene therapy intervention.
22. Walking for exercise at a level comparable to that targeted in our intervention.
23. Current participation in or completion of a cardiac rehabilitation program within the last six months.

    The following exclusion criteria will be assessed at the time of the study visit or later:
24. Severe aortic stenosis identified by physical exam at the study visit.
25. Critical limb ischemia identified by physical exam at the study visit.
26. Coronary ischemia during exercise, defined as ST segment depression \> 1 mm during the baseline exercise treadmill test, with or without associated chest discomfort, without a perfusion stress test demonstrating no reversible ischemia within the previous 3 months.
27. Left-bundle branch block or significant ST-T wave changes on the baseline ECG without a perfusion stress test demonstrating no reversible ischemia within the previous 3 months.
28. Stopping during the treadmill stress test for shortness of breath, chest pain, hip pain, knee pain, or another symptom that may not represent ischemic leg pain.
29. Stopping during the six-minute walk test for symptoms other than ischemic leg symptoms.
30. Foot ulcer identified at the study visit.
31. Mini-Mental Status Examination (MMSE) score \< 23 or disabling psychiatric disease.
32. Failure to complete a study run-in period.
33. Walking impairment due to a cause other than PAD.

In addition to the exclusion criteria listed above, individuals thought to be poorly suited to the intervention (i.e. not a good fit) can be excluded at the discretion of the principal investigator.
B: Inclusion Criteria:

* AST, ALT, alkaline phosphatase and bilirubin less than and equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including \[medical history, physical examination and laboratory tests\]. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk and will not interfere with the study procedures.
* A hemoglobin value at screening between 13.5- 16 g/dL.
* Male subjects between 18 and 55 years of age inclusive, at the time of signing the informed consent.
* Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
* BMII less than and equal to 32 kg/m2
* Single QTcB or QTcF less than 450 msec
* Screening echocardiogram of at least good quality, without clinically significant abnormalities, and with mild-moderate tricuspid regurgitation sufficient for the reliable estimation of PASP, as determined by the echocardiography core laboratory or responsible cardiologist.
* Screening PASP within the normal range under normoxic conditions.

Exclusion Criteria:

* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result.
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* A positive pre-study drug/alcohol screen.
* Any history of IV drug abuse.
* A positive test for HIV antibody.
* History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 14 drinks for males or greater than 7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
* Strong family history of malignancy.
* Subjects with sickle cell trait.
* History of pulmonary hypertension
C: 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
D: Inclusion Criteria:

* Having peripheral artery disease at the stage of Critical Limb Ischemia (CLI) with skin lesions (either ulcer(s) or gangrene);
* With objective evidence of CLI such as ankle systolic pressure \<70 mmHg and/or toe systolic pressure \<50 mmHg or transcutaneous oxygen pressure (TcPO2) \<30 mmHg;
* Unsuitable for standard revascularization of his/her peripheral arterial disease;
* Having a negative screening for cancer.

Exclusion Criteria:

* Previous major amputation on the leg to be treated or planned major amputation within the first month following randomization;
* Known Buerger's disease;
* Successful lower extremity revascularization procedure within 3 months prior randomization;
* Uncontrolled blood pressure defined as systolic blood pressure (SBP) ≥180 mmHg or diastolic blood pressure (DBP) ≥110 mmHg despite adequate antihypertensive treatment;
* Acute cardiovascular events within 3 months prior to randomization;
* Active proliferative retinopathy and severe macular oedema;
* Previous or current history of malignant disease within the past 5 years;
* Previous treatment with systemic angiogenic factors or with stem cells therapy;
* Pregnant or breast-feeding woman or woman of childbearing potential not protected by an effective contraceptive method of birth control. Man not following effective contraceptive method with his partner of childbearing potential during the course of the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Answer: C