Please select the eligibility criteria that correspond to the clinical trial below.
Title: Evaluation of the Effect of Ambrisentan on Digital Microvascular Flow in Patients With Systemic Sclerosis Using Laser Doppler Perfusion Imaging
Brief Summary: The purpose of this study is to investigate the effectiveness of a drug called ambrisentan, approved by the FDA for use in pulmonary hypertension (a condition where there is increased pressure in the right side of the heart) in scleroderma patients, to see if this medicine may be beneficial in relieving and/or preventing Raynaud's flares in you and other patients like you. This medicine may have some short-term and long-term benefits in persons with scleroderma


Options:
A: Inclusion Criteria:

* At least 12 years of age.
* Body weight at least 40 kg (approximately 88 pounds).
* Pulmonary hypertension (PAH) that is either idiopathic; related to collagen vascular disease; related to anorexigen use; associated with an atrial septal defect (resting SaO2 greater than or equal to 88%); with surgical repair, of at least 1 year duration, of a congenital systemic-to-pulmonary shunt.
* If on bosentan, must be at the maximal dose of 125 mg twice daily for a minimum of 12 weeks prior to screening and have an AST/ALT less than 3 times normal.
* History of PAH established by a resting mean pulmonary artery pressure greater than or equal to 25 mm Hg, pulmonary artery wedge pressure less than or equal to 15 mm Hg, and pulmonary vascular resistance greater than or equal to 3 Wood units via right heart catheterization
* Have World Health Organization functional class I, II, III or IV status.
* Have a qualifying 6-minute walk test distance at screening
* Have no evidence of significant parenchymal lung disease

Exclusion Criteria:

* Are nursing or pregnant.
* PAH due to conditions other than noted in the above inclusion criteria.
* History of left-sided heart disease.
* History of atrial septostomy within 3 months before study entry
* History of angina pectoris or other condition that was treated with long-or short-acting nitrates within 12 weeks before administration of study drug.
* History of symptomatic coronary disease.
* Have any therapy with a prostacyclin or analogue, L-arginine, phosphodiesterase (PDE) inhibitor, or investigational drug within 4 weeks before administration of study drug.
B: Inclusion Criteria:

* Symptomatic pulmonary hypertension in modified NYHA functional class II to IV due to CTEPH as demonstrated by ventilation/perfusion lung scanning and pulmonary angiography.
* CTEPH judged inoperable because of peripheral localization of thrombotic material or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) with no evidence of recurrent thromboembolism and not amenable to repeated surgery.
* 6-minute walk test (6MWT) distance \< 450 m.
* Hemodynamic evaluation showing: Mean pulmonary arterial pressure (mPAP) \>= 25 mmHg; Pulmonary capillary wedge pressure (PCWP) \< 15 mmHg; Pulmonary vascular resistance (PVR) at rest \>= 300 dyn×sec/cm5
* For patients who underwent PEA, hemodynamic evaluation must have been performed more than 6 months after PEA.
* For all patients, hemodynamic evaluation must have been performed with the 3 months immediately preceding inclusion.
* Men or women \>= 18 and =\< 80 years of age (Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception).
* Anticoagulants at efficacious dose for at least 3 months prior to randomization.
* Signed informed consent prior to initiation of any study-mandated procedure.

Exclusion Criteria:

* Other forms of pulmonary hypertension including pulmonary hypertension related to sickle cell disease.
* Obstructive lung disease: FEV1/FVC \< 0.5 after bronchodilator.
* Severe restrictive lung disease: Total Lung Capacity \< 60% of predicted value.
* Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements (in particular with 6MWT), e.g., angina pectoris, intermittent claudication.
* Symptomatic pulmonary embolism within 6 months prior to randomization.
* Pulmonary endarterectomy within 6 months prior to randomization.
* Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
* Illness with a life expectancy of less than 6 months.
* Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
* AST and/or ALT \> 3 times the upper limit of normal ranges.· Hemoglobin concentration \< 75% the lower limit of normal ranges.
* Pregnancy or breast-feeding.
* Systolic blood pressure (BP) \< 85 mmHg.
* Treatment or planned treatment with another investigational drug and/or pulmonary angioplasty within 3 months prior to randomization.
* Treatment with an endothelin receptor antagonist, a phosphodiesterase inhibitor, L-arginine or with prostanoids (excluding acute administration during a catheterization procedure to test vascular reactivity) within 3 months prior to randomization.
* Treatment for pulmonary hypertension within 1 month prior to randomization, excluding calcium channel blockers if present for at least 1 month before randomization.
* Treatment with calcineurin-inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus, fluconazole, glibenclamide (glyburide) within 1 week prior to randomization.
* Known hypersensitivity to bosentan or any of the excipients.
C: Inclusion Criteria:

* Subjects should have limited scleroderma with disease duration \<7 years and should satisfy American College of Rheumatology criteria for diagnosis.9;
* 10 Raynaud's phenomenon would be defined as episodic, bilateral, digital color changes (at least 2 out of 3 possible phases:

  * pallor, cyanosis, rubor),
  * provoked by cold or emotional stress.
* Subjects should be between 18 and 70 years of age and be able to give informed consent.

Exclusion Criteria:

* (a) current tobacco users,
* (b) advanced cardiopulmonary disease,
* (c) clinically unstable patient,
* (d) presence of active digital ulcers or prior history of digital ulcers which led to scarring or significant pitting of digits in the area of interest(presence of ulcers or pits would interfere with measurement of blood flow by LDPI),
* (e) pregnancy (class X in pregnancy) or unable to use two reliable forms of contraception during the study if patient is of child bearing age,
* (f) patients with moderate or severe hepatic impairment
* (g) hemoglobin values less than 10% of the lower limit of normal per laboratory standards
* (h) inability to discontinue vasodilator treatment including calcium channel blockers, nitrates, alpha blockers, PDE-5 inhibitors, ACE inhibitors and angiotensin receptor blockers at least one week prior to the study,
* (i) echocardiographic evidence of pulmonary arterial hypertension \[estimated right ventricular systolic pressure \<35 mm Hg\],
* (j) based on section 7.3 of the full prescribing information booklet- patients on cyclosporine, rifampin or ritonavir should be excluded,
* (k) patients with diffuse disease,
* (l) disease duration \> 7 years
D: Main inclusion criteria:

* Systemic Sclerosis diffuse or limited
* Significant Interstitial Lung Disease on HRCTscan
* DLco \< 80% predicted
* Dyspnea on exertion
* Walk not limited by musculoskeletal reasons

Main exclusion criteria:

* Interstitial Lung Disease due to other conditions than SSc
* End stage restrictive or obstructive lung disease
* Severe cardiac or renal diseases
* Significant pulmonary arterial hypertension
* Smoker (\> 5cig./day)
* Treatment with immunosuppressive, antifibrotic drugs, high dose corticosteroids (within 4 weeks of randomization)

Answer: C