REstoration of VItamin D in Pulmonary Arterial Hypertension

NCT06258850 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: ICI23/00001
• Study Type: interventional
• Target: 102
• Locations: 0 countries
• Sites: N/A

Brief 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

Keywords

Clinical improvement; Clinical worsening

Outcome Measures

Primary Outcomes (1)

• Clinical improvement without clinical worsening

  Clinical improvement is defined as a change in at least two of the following variables: 1) increase in 6 minutes walking distance (6MWD) \>= 10% or more than 30 m, 2) change from intermediate-low or intermediate-high risk to low risk score or change from intermediate-high to intermediate-low risk according to 2022 ERS/ESC guidelines), 3) reduction in BNP or NT-proBNP \>= 30%, 4) increase in the TAPSE/SPAP ratio \>= 25%. Clinical worsening is defined as any of the following events: a) hospitalization related to PAH, b) therapeutic escalation, c) progression of symptoms, d) lung or cardiopulmonary transplantation, e) atrial septostomy and f) mortality related to PAH.

  24 weeks

Secondary Outcomes (7)

• 6 minute walking distance

  24 weeks

• serum BNP or nt-pro-BNP

  24 weeks

• functional class (WHO/NYAS)

  24 weeks

• noninvasive risk score (NIRS) based on the three previous variables

  24 weeks

• ventricular function analyzed echocardiographically by TAPSE

  24 weeks

Study Arms (2)

Calcifediol

EXPERIMENTAL

Calcifediol (25-OH vitamin D3) in oral soft capsules (Hidroferol® 0,266 mg, equivalent to 15960 IU vitamin D).

Drug: Calcifediol Oral Capsule

Placebo

PLACEBO COMPARATOR

Placebo in oral soft capsules (externally indistinguishable from Hidroferol®).

Drug: Placebo

Interventions

Calcifediol Oral Capsule DRUG

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.

Also known as: Vitamin D

Calcifediol

Placebo DRUG

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

Also known as: Control

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 vitamin D, defined herein as plasma or serum 25(OH)vitamin D 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.

You may not qualify if:

• Participation in another interventional clinical study within 30 days before screening.
• Previous randomisation to treatment during this study (no re-randomisation).
• Pregnant women or breastfeeding women, or women with childbearing potential not using a effective contraception method throughout the study.
• 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 with substance abuse (eg, alcohol or drug abuse) within the previous 3 months before and at randomisation.
• Patients with underlying medical disorders with an anticipated life expectancy \<2 years.
• Patients with a history of severe allergies or multiple drug allergies or with hypersensitivity to the investigational drug or any of the excipients.
• Patients unable to perform a valid 6MWD test (eg, orthopaedic disease or peripheral artery occlusive disease that affects the patient's ability to walk).
• Excluded medication/treatment: active treatment with digoxin.

Sponsors & Collaborators

• Parc de Salut Mar: lead
• Universidad Complutense de Madrid: collaborator
• Hospital Clinic of Barcelona: collaborator
• Hospital Vall d'Hebron: collaborator
• Hospital Universitario Marqués de Valdecilla: collaborator
• Hospital Universitario de Gran Canaria Doctor Negrín: collaborator
• Hospital Universitario La Fe: collaborator
• Hospital Universitario Doctor Peset: collaborator
• Hospital Universitario Ramon y Cajal: collaborator
• Hospitales Universitarios Virgen del Rocío: collaborator

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension; Vitamin D Deficiency

Interventions

Calcifediol; Vitamin D

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Diego A Rodríguez Chiaradía, MD PhD

  Hospital del Mar

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diego A Rodríguez Chiaradía, MD PhD

CONTACT

+34922483548; darodriguez@psmar.cat

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo capsules will be identical to those of the active treatment. The batch of capsules for each patient will be codified and codes will be provided by the producing company to the SCReN platform who will keep them so that patients and investigators and the local pharmacy will be blind.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD. Head of Pneumology Department

Model Details: Multicenter clinical trial, placebo-controlled, randomized (1:1 ratio), in two parallel groups (without crossover), cuadruple blind, and add-on on existing treatments.

Study Record Dates

• First Submitted: February 6, 2024
• First Posted: February 14, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 14, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Up to 5 years after the end of the study
• Access Criteria: Data will be shared upon request either for collaborative purposes or whenever the researcher has reasonable questions about the study.