Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03416361 |
| Other study ID # |
224168 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2023 |
| Est. completion date |
March 1, 2027 |
Study information
| Verified date |
October 2022 |
| Source |
University of Leeds |
| Contact |
Klaus K Witte, MD |
| Email |
k.k.witte[@]leeds.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
VINDICATE 2 will be a randomised, placebo-controlled, parallel group, double-blind study of
vitamin D versus placebo in otherwise optimally-managed patients with CHF due to LVSD and
vitamin D deficiency (<50nmol/L). The intervention will be a daily dose of 4000IU (100µg) per
day or matching placebo for a minimum of 2 years and a maximum of 4 years.
Description:
DESIGN: Multi-centre, phase III, double-blind, parallel-group, placebo-controlled trial.
SETTING: Secondary care heart failure clinics across the UK. TARGET POPULATION: Higher-risk
patients with CHF due to LVSD recruited from CHF clinics.
HEALTH TECHNOLOGY: 4000IU (100mcg) vitamin D3 or placebo daily for minimum 2yrs and maximum
4yrs.
MEASUREMENT OF OUTCOMES:
Primary end-point is a composite of HF hospitalisation or death Secondary outcomes include
all-cause mortality, hospitalisations and cost-effectiveness. Patient outcomes will be
obtained from NHS Digital (KKW is an approved researcher) with a transfer of linked data to
be held at the Leeds Institute for Data Analysis.
Patient reported outcomes will be Minnesota Living with HF questionnaire and EQ-5D which will
be assessed at twelve-monthly research visits.
SAMPLE SIZE: Based on VINDICATE, 2-yr CV mortality or hospitalisation in stable high-risk HF
is 28% in those receiving placebo and 21% in those receiving vitamin D3 (hazard ratio 0.717).
In the largest observational study (n=1800) of the effect of vitamin D deficiency on outcomes
in patients with CHF on optimal medical therapy, balanced for all important variables except
vitamin D, there was a significant adverse effect of vitamin D deficiency on all-cause
mortality, demonstrating a 14% reduction in death for each 2.72-fold increase in vitamin D.
To demonstrate this effect 379 events in 1278 patients are required. Calculations assume time
to CV event follows an exponential distribution, 2-sided 5% level of significance, 90% power,
20% dropout, 2.5-yrs recruitment and min. 2-yr follow-up.
ANALYSIS: Primary analysis will be on an intention-to-treat basis. Cox proportional hazards
regression will be fitted to the time to first CV event adjusted for stratification factors.
Health Economics: A model will estimate lifetime incremental costs from an NHS/PSS
perspective and QALYs gained based data from VINDICATE-2 and the literature. ICERs will be
estimated and compared to standard cost-effectiveness thresholds to determine if vitamin D3
supplementation is cost-effective. Further analyses will explore the value of investing in
activities to support uptake of vitamin D3 in clinical practice.
CURRENT AND PLANNED CARE PATHWAYS: The pathway within the study will be 4000IU vitamin D3
daily or placebo followed by safety and adherence visits at 3m and 12 monthly
post-randomisation up to final visit at 24-48m. Patients will be screened, recruited and
followed up during standard clinic visits. A small parcel containing three months of the
intervention will be posted to participants by Leeds Teaching Hospitals Pharmacy every three
months for the duration of their involvement in the study.
If adopted into standard care pathways, vitamin D could be prescribed and monitored cheaply
and easily in primary care with annual blood tests.
PROJECT TIMETABLES: Set-up 6m, recruitment 30m, follow-up 24m, data cleaning, analysis and
reporting 6m - total 66m.
RECRUITMENT RATE: 5 main centres (+2 PIC sites), 3.55 pts/mth/centre.
