In short
Calcifediol monohydrate is a vitamin D3 analog and the major circulating form of vitamin D in the body. It is already authorised in some countries as an extended-release capsule for secondary hyperparathyroidism in adults with chronic kidney disease. A Phase 3 clinical trial is now investigating whether calcifediol monohydrate can reduce myocardial fibrosis in 152 patients with acute myocarditis.
Key points
- Calcifediol monohydrate is a vitamin D3 analog already authorised for secondary hyperparathyroidism in chronic kidney disease.
- A Phase 3 trial is testing it in acute myocarditis with myocardial fibrosis.
- The trial plans to enroll 152 participants and is currently authorised.
- The primary outcome is extent of late gadolinium enhancement (LGE) on cardiac MRI at 6 months.
- Calcifediol is produced in the liver and is the best indicator of the body's vitamin D stores.
- The authorised product is given as extended-release capsules taken orally once daily.
What is calcifediol monohydrate?
Calcifediol monohydrate is a vitamin D3 analog, also known as calcifediol, calcidiol, or calderol. It is the major circulating metabolite of vitamin D3, produced in the liver, and is considered the best indicator of the body's vitamin D stores. In the United States, calcifediol is authorised as an extended-release capsule under the trade name Rayaldee for the treatment of secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. The product is supplied by OPKO Pharmaceuticals LLC and received initial US approval in 2016.
How does calcifediol monohydrate work?
Calcifediol monohydrate is a prohormone of the active hormone calcitriol. As the major circulating form of vitamin D3, it is converted in the kidneys to the active hormone that regulates calcium and phosphate balance in the body. In chronic kidney disease, reduced kidney function leads to lower production of active vitamin D, which in turn raises parathyroid hormone levels, causing secondary hyperparathyroidism. Supplementing calcifediol helps restore vitamin D levels and reduce parathyroid hormone overactivity. The current Phase 3 trial is based on a different rationale: patients with acute myocarditis and low vitamin D levels may have more myocardial fibrosis, and vitamin D supplementation could reduce the scarring of heart muscle.
Which conditions is it used or studied for?
- Secondary hyperparathyroidism in chronic kidney disease — the authorised indication for the extended-release capsule in adults with stage 3 or 4 chronic kidney disease and low vitamin D levels.
- Acute myocarditis — a Phase 3 trial is studying whether calcifediol monohydrate can reduce myocardial fibrosis after an episode of uncomplicated acute myocarditis.
- Myocardial fibrosis — scarring of the heart muscle, measured by late gadolinium enhancement on cardiac MRI, is the main outcome of the ongoing trial.
How is calcifediol monohydrate given?
The authorised product is an extended-release capsule for oral use, available in a 30 mcg strength. The initial dose in the prescribing information is 30 mcg taken orally once daily at bedtime, with the possibility of increasing to 60 mcg once daily after 3 months based on laboratory values. In the clinical trial for acute myocarditis, calcifediol monohydrate is given orally at a dose of 266 micrograms.
What do the clinical trials show?
One Phase 3 interventional trial, registered in the EU Clinical Trials Information System as 2025-523092-33-00, is currently authorised and plans to enroll 152 participants. The trial evaluates the effect of vitamin D supplementation on myocardial fibrosis at 6 months follow-up, assessed by late gadolinium enhancement on cardiac MRI, in patients with uncomplicated acute myocarditis and low levels of 25-hydroxyvitamin D.
What is the trial measuring?
The primary outcome is the extent of late gadolinium enhancement (LGE), expressed as a percentage of left ventricle mass, at month 6. LGE on cardiac MRI shows areas of scarred or fibrotic heart muscle. The analysis is performed by a central core laboratory in a blinded manner to reduce bias.
Who can take part in this trial?
The trial includes patients with uncomplicated acute myocarditis who have low levels of 25-hydroxyvitamin D. The register does not list further detailed inclusion or exclusion criteria in the available summary.
What side effects are known?
The prescribing information for the authorised extended-release capsule warns that excessive administration of vitamin D compounds, including calcifediol, can lead to hypercalcemia, a condition of elevated calcium in the blood. No further details on side effects are provided in the available sources.