REstoration of VItamin D in Pulmonary Arterial Hypertension

Summary

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.

Conditions

• Pulmonary Artery Hypertension
• Vitamin d Deficiency

Interventions

DRUG

Calcifediol Oral Capsule

One Hydroferol® soft capsule (0.266 mg) will be administered once weekly for the first 12 weeks and one capsule every two weeks for the next 12 weeks.

DRUG

Placebo

One soft capsule will be administered once weekly for the first 12 weeks and one capsule every two weeks for the next 12 weeks.

Sponsors & Collaborators

• Universidad Complutense de Madrid

  collaborator OTHER

• Hospital Clinic of Barcelona

  collaborator OTHER

• Hospital Vall d'Hebron

  collaborator OTHER

• Hospital Universitario Marqués de Valdecilla

  collaborator OTHER

• Hospital Universitario de Gran Canaria Doctor Negrín

  collaborator UNKNOWN

• Hospital Universitario La Fe

  collaborator OTHER

• Hospital Universitario Doctor Peset

  collaborator OTHER

• Hospital Universitario Ramon y Cajal

  collaborator OTHER

• Hospitales Universitarios Virgen del Rocío

  collaborator OTHER

• Parc de Salut Mar

  lead OTHER

Principal Investigators

• Diego A Rodríguez Chiaradía, MD PhD · Hospital del Mar

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-01

Primary Completion

2027-06-30

Completion

2027-12-31