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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorci Mar Parc De Salut De Barcelona

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-09-02

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To analyze whether a vitamin D supplement (0,266 mg calcifediol, once every ten days for the first 12 weeks and once every two weeks in the following 12 weeks) induces clinical improvement without clinical worsening at week 24 compared with placebo. 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-2 low or intermediate-high risk to low risk score or change from intermediate-high to intermediatelow 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.

Secondary objectives 9

1. Changes in 6MWD
2. Changes in NT-proBNP
3. Changes in functional class (WHO/NYAS)
4. Changes in estimated pulmonary systolic pressure (PASP)
5. Changes in TAPSE/PASP
6. Changes in serum noggin levels
7. Changes in non-invasive risk score (NIRS)
8. Changes in quality of life (emPHasis-10)
9. Changes in adverse effects. Other variables such as plasma intact parathormone (i-PTH), calcium and phosphate will be also analyzed and compared at baseline, 12 weeks and at the end of the treatment period

Conditions and MedDRA coding

Patients with diagnosis of Pulmonary Arterial Hypertension of the following types according to 2022 ERS/ESC guidelines: idiopathic, hereditary, drug- and toxin-induced PAH or associated to connective tissues disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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 vitD, defined herein as plasma or serum 25(OH)vitD 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 15

1. Participation in another interventional clinical study within 30 days before screening.
2. Previous randomization to treatment during this study (no re-randomization).
3. Pregnant women or breastfeeding women, or women with childbearing potential not using an 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.
10. Exclusion criteria related to pulmonary disease: a. All types of PH except subtypes of PAH specified in the inclusion criteria. b. Evidence of clinically significant restrictive or obstructive parenchymal lung diseases in the judgement of the investigator. c. Severe congenital abnormalities of the lungs, thorax, and diaphragm. d. Severe restrictive lung disease (total lung capacity <60%). e. Moderate obstructive lung disease (forced expiratory volume in 1 second/forced vital capacity <50%). f. Confirmed obstructive sleep apnoea. g. Severe diffusion impairment (DLCO <30% predicted). h. History or active state of serious haemoptysis/pulmonary haemorrhage, including those managed by bronchial artery embolisation
11. Exclusion criterion related to hypoxia (pulse oximeter at rest): Peripheral capillary oxygen saturation <88% despite supplemental oxygen therapy (≤4 L/min) at rest.
12. 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.
13. Exclusion criteria related to disorders in organ function: a. Clinically relevant hepatic dysfunction indicated by: i. Bilirubin >2 times ULN, and/or ii. Alanine aminotransferase or aspartate aminotransferase >3 times upper limit of normal. b. Signs of severe hepatic insufficiency (Child -Pugh C), and/or c. Renal insufficiency. a. Other co-morbidities impairing exercise capacity.
14. Previous diagnosis of osteoporosis, osteomalacia or other alterations of calcium or phosphorus homeostasis.
15. Active treatment with vitD supplements, bisphosphonates, calcitonin, parathormone or mitramicine.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy outcome: clinical improvement and no clinical worsening.

Secondary endpoints 10

1. Safety of the intervention: Serum 25(OH) vitD concentration
2. Six minute walk text (6MWD)
3. Plasmatic levels of N-terminal pro b-type natriuretic peptide (NT-proBNP)
4. Functional class (WHO/NYAS)
5. Estimated pulmonary systolic pressure (PASP)
6. TAPSE/PASP: the ratio of Tricuspid Annular Plane Systolic Excursion (TAPSE) to Pulmonary Arterial Systolic Pressure (PASP)
7. Serum noggin protein level.
8. Non-invasive risk score (NIRS) (FC,6MWT and NT-proBNP).
9. Quality of life (emPHasis-10).
10. Adverse effects.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorci Mar Parc De Salut De Barcelona

Sponsor organisation

Consorci Mar Parc De Salut De Barcelona

Address

Passeig Maritim De La Barceloneta 25-29

City

Barcelona

Postcode

08003

Country

Spain

Scientific contact point

Organisation

Consorci Mar Parc De Salut De Barcelona

Contact name

Diego Rodriguez Chiaradia

Public contact point

Organisation

Consorci Mar Parc De Salut De Barcelona

Contact name

Ana María Aldea Perona

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications