REstoration with calcifediol of VItamin D deficiency in pulmonary Arterial Hypertension patients (REVIDAH study)

Prior treatment

• Participation in another interventional clinical study within 30 days before screening.
• Exclusion criterion related to hypoxia (pulse oximeter at rest): Peripheral capillary oxygen saturation <88% despite supplemental oxygen therapy (≤4 L/min) at rest.
• Cardiovascular exclusion criteria: a. Uncontrolled arterial hypertension (systolic blood pressure (SBP) >180 mm Hg and/or diastolic BP (DBP) >110 mm Hg). b. SBP <95 mm Hg before and at randomisation. c. Resting heart rate in the awake patient <50 bpm or >105 bpm. d. Permanent atrial fibrillation and new onset of atrial fibrillation within the 3 months before screening. e. Left ventricular systolic dysfunction by echocardiography (<40%, Simpson's methodology). f. Hypertrophic obstructive cardiomyopathy. g. Severe proven or suspected coronary artery disease. h. Clinical evidence of symptomatic atherosclerotic disease. i. History of stroke within 3 months before and at randomisation. j. Congenital or acquired valvular or myocardial disease if clinically significant apart from tricuspid valvular insufficiency due to PAH. k. Three or more of the following left ventricular disease/dysfunction risk factors: i. Body mass index≥30 kg/m2, ii. History of essential hypertension, iii. Diabetes mellitus of any type, iv. History of significant coronary disease.
• Active treatment with vitD supplements, bisphosphonates, calcitonin, parathormone or mitramicine.
• Previous randomization to treatment during this study (no re-randomization).
• Patients with substance abuse (eg, alcohol or drug abuse) within the previous 3 months before and at randomisation.
• Patients with a history of severe allergies or multiple drug allergies or with hypersensitivity to the investigational drug or any of the excipients.
• Excluded medication/treatment: active treatment with digoxin.

Other illness

• Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate in or complete this study, in the opinion of the investigator.
• Patients unable to perform a valid 6MWD test (eg, orthopaedic disease or peripheral artery occlusive disease that affects the patient's ability to walk).

Lab values

• Previous diagnosis of osteoporosis, osteomalacia or other alterations of calcium or phosphorus homeostasis.

Age

• Patients with underlying medical disorders with an anticipated life expectancy <2 years.

Other

• Pregnant women or breastfeeding women, or women with childbearing potential not using an effective contraception method throughout the study.

• Male and female patients aged 18 -75 years.
• Patients with diagnosis of PAH of the following types according to 2022 ERS/ESC guidelines: idiopathic, hereditary, drug- and toxin-induced PAH or associated to connective tissues disease.
• Patients who are stable and treated with standard medications for PAH on monotherapy or with combinations of drugs, including calcium channel blockers, phosphodiesterase type 5 inhibitors (PDE5i), endothelin receptor antagonists (ERA), prostacyclin analogues or selexipag or with stable dose of diuretics who had no treatment modification for at least 6 weeks before randomization.
• Patients with an intermediate-low and intermediate-high risk score according to 2022 ERS/ESC guidelines.
• Patients with severe deficiency of vitD, defined herein as plasma or serum 25(OH)vitD levels equal to or lower than 12 ng/ml.
• Patients who can understand and follow instructions, and who are able to participate in the study for the entire study.
• Patients must have given their written informed consent to participate in the study after having received adequate previous information and before any study-specific procedures.