REstoration With Calcifediol of VItamin D Deficiency in Pulmonary Arterial Hypertension Patients

ICI23/00001

Background. Pulmonary arterial hypertension (PAH) is a heterogeneous pathophysiological condition characterized by progressive pulmonary vascular narrowing that ultimately results in right-sided heart failure and eventually death or lung transplantation. The effectiveness of current pharmacological treatments is suboptimal and a large proportion of patients still had events or died despite receiving combination therapy. Vitamin D deficiency has been found to be much more frequent in PAH patients than in the general population or even compared to patients with other severe cardiovascular diseases. Moreover, vitamin D deficiency has a negative prognostic impact in PAH. Animal studies support that vitamin D deficiency worsens PAH. Hypothesis. In patients with PAH and vitamin D deficiency, restoration of vitamin D status with calcifediol improves their symptomatology and prognosis. Design: Multicenter clinical trial with the participation of 9 hospitals, placebo-controlled, randomized (1:1 ratio), in two parallel groups (without crossover), triple blind, and add-on on existing treatments (add-on). It will include at least 102 subjects (51 in the calcifediol group and 51 in the placebo group) followed for 24 weeks of treatment. Inclusion criteria: Patients of both sexes (18-75 years) with hemodynamic diagnosis of PAH and severe vitamin D deficiency (25-OHvitD \<= 12 ng/ml) and without previous diagnosis of osteoporosis or osteomalacia. Treatments: 1) Calcifediol Hydroferol® 0.266 mg once every 10 days for the first 12 weeks and once every two weeks for the following 12 weeks. 2) Placebo. Main objective: A composite endpoint of clinical improvement without clinical worsening at week 24. Expected outcome: Restoration of vitamin D status is an unexpensive measure, very easily implantable and that could improve the evolution of the disease as well as other aspects such as bone or immune health and that has few side effects.

2024-07-01

2027-06-01

2027-12-01

Not yet recruiting

Early phase I

102

Inclusion Criteria: 1. Male and female patients aged 18 -75 years. 2. 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. 3. 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. 4. Patients with an intermediate-low and intermediate-high risk score according to 2022 ERS/ESC guidelines. 5. Patients with severe deficiency of vitamin D, defined herein as plasma or serum 25(OH)vitamin D levels equal to or lower than 12 ng/ml 6. Patients who can understand and follow instructions, and who are able to participate in the study for the entire study. 7. 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. Exclusion Criteria: 1. Participation in another interventional clinical study within 30 days before screening. 2. Previous randomisation to treatment during this study (no re-randomisation). 3. Pregnant women or breastfeeding women, or women with childbearing potential not using a effective contraception method throughout the study. 4. 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. 5. Patients with substance abuse (eg, alcohol or drug abuse) within the previous 3 months before and at randomisation. 6. Patients with underlying medical disorders with an anticipated life expectancy \<2 years. 7. Patients with a history of severe allergies or multiple drug allergies or with hypersensitivity to the investigational drug or any of the excipients. 8. Patients unable to perform a valid 6MWD test (eg, orthopaedic disease or peripheral artery occlusive disease that affects the patient's ability to walk). 9. Excluded medication/treatment: active treatment with digoxin.

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2024-02-14