Clinical Trial Results:
Vitamin D Supplementation on Assisted Reproduction Technology (ART) outcomes: a
randomized clinical controlled trial and an investigation of the involved biological mechanisms
Summary
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EudraCT number |
2015-004233-27 |
Trial protocol |
IT |
Global end of trial date |
31 Dec 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Jul 2021
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First version publication date |
23 Jul 2021
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Other versions |
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Summary report(s) |
Manuscript AJOG |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RF-2013-02358757
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
SUNDRO: - | ||
Sponsors
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Sponsor organisation name |
FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
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Sponsor organisation address |
via Sforza 35, Milan, Italy,
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Public contact |
U.O.S.D. CENTRO P.M.A., FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO, 0039 0255036582, centrosterilita@policlinico.mi.it
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Scientific contact |
U.O.S.D. CENTRO P.M.A., FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO, 0039 0255036582, centrosterilita@policlinico.mi.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Apr 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
the study aims at determining the potential benefits of vitamin D supplementation in improving clinical pregnancy rate in womenundergoing ART
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Protection of trial subjects |
no particular concerns regarding pain or distress related to the protocol.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 May 2016
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
24 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 630
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Worldwide total number of subjects |
630
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EEA total number of subjects |
630
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
630
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Women undergoing IVF with or without intracytoplasmic sperm injection (ICSI) at the infertility units of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and IRCCS San Raffaele Scientific Institute between October 2016 and January 2019 were considered for study entry. Recruitment was consecutive. | |||||||||
Pre-assignment
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Screening details |
Evauated 2450 subjetcs; Eligile 1128 subjects; enrolled 630 subjects. | |||||||||
Period 1
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Period 1 title |
first (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Investigator, Monitor, Data analyst, Subject | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Vitamin D | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
DBase
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Investigational medicinal product code |
36635035
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Other name |
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Pharmaceutical forms |
Oral drops, solution
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Routes of administration |
Oral use
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Dosage and administration details |
Supplementation was given as a single
administration of oral 600,000 IU of
vitamin D3 to ensure maximal adherence.
This modality is expected to
properly maintain peripheral levels of
vitamin D above 30 ng/mL for 3
months,
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Arm title
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Placebo | |||||||||
Arm description |
- | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
placebo olive oil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution in single-dose container
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo was given as a single
administration of oral olive oil.
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Baseline characteristics reporting groups
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Reporting group title |
Vitamin D
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Pregnancy rate
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
IVF cycle outcome in the 2 study groups
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Subject analysis set title |
Supplemented
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
women receiving vitamin D
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Subject analysis set title |
Placebo
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Women receiving placebo
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End points reporting groups
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Reporting group title |
Vitamin D
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
- | ||
Subject analysis set title |
Pregnancy rate
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
IVF cycle outcome in the 2 study groups
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Subject analysis set title |
Supplemented
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
women receiving vitamin D
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Subject analysis set title |
Placebo
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Women receiving placebo
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End point title |
Pregnancy rate | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
5 weeks after last treatment
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Statistical analysis title |
Clinical pregnancy rate | ||||||||||||||||||||||||
Statistical analysis description |
cumulative clinical pregnancy rate
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Comparison groups |
Vitamin D v Placebo
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Number of subjects included in analysis |
630
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.37 | ||||||||||||||||||||||||
Method |
Chi-squared | ||||||||||||||||||||||||
Parameter type |
Risk ratio (RR) | ||||||||||||||||||||||||
Point estimate |
0.91
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.75 | ||||||||||||||||||||||||
upper limit |
1.11 |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Only maternal events occurring within 3 months from randomization were considered because a single dose of 600,000 IU is expected to
raise peripheral levels for no more than 3 months.
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Adverse event reporting additional description |
Given the well-known pharmacologic and safety profile of vitamin D3, we did not deem necessary a strict monitoring
of the included women, and only severe adverse events were recorded (death, life-threatening conditions, new
or prolonged hospitalization, persistent or relevant disability, or congenital anomalies).
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
vitamin D
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Reporting group description |
- | ||||||||||||||||||||||||||||||
Reporting group title |
placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Given the well-known pharmacologic and safety profile of vitamin D3,17,22 we did not deem necessary a strict monitoring of the included women, and only severe adverse events were recorded (death, life-threatening conditions, new or prolonged hospitalization, persistent or relevant disability, or congenital anomalies). |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/3389415 |