Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?

• Sponsor: Shahid Beheshti University of Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT04323852
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.7
• Patients Per Site Per Month: 4.2

Study Details

Study Description

Brief Summary

Background and study aim:

Heart diseases are among the most common causes of death worldwide. A large proportion of deaths are caused by heart attacks (myocardial infarction), where blood flow to the heart is reduced resulting in damage to the heart muscle. If the arteries supplying blood to the heart start to become blocked, Coronary Artery Bypass Grafting (CABG) surgery is a treatment to replace the blocked sections of artery can reduce angina (chest pain). However, CABG surgery has complications, including an increased risk of heart attack. Vitamin D deficiency is thought to be linked to poorer recovery from heart attack and CABG surgery. This study aims to investigate if vitamin D supplementation can reduce injury to the heart following CABG surgery.

Who can participate? Adults with vitamin D deficiency undergoing CABG

What does the study involve? Participants are randomly allocated to one of two groups. Those in the first group receive vitamin D at 3 doses per day for 3 days before surgery. The second group will receive a dummy pill (placebo). Both groups will have standard CABG surgery.

What are the possible benefits and risks of participating? Those in the vitamin D group might benefit from its effects. Vitamin D has few side effects, especially when taken for only a few days.

Where is the study run from? Shahid Modarres Hospital (Iran)

When is the study starting and how long is it expected to run for? September 2017 to January 2019

Who is funding the study? Deputy of Research of Shahid Beheshti School of Medicine

Who is the main contact? Dr Erfan Tasdighi [e-mail]

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency; Cardiomyopathies; Apoptosis; Inflammation	Drug: Vitamin D; Drug: Placebo	Phase 4

Detailed Description

Enrollment started in June 2018 and was completed in December 2018. The inclusion criteria were as following: the patients referred for elective and isolated Coronary Artery Bypass Graft (CABG) using Cardiopulmonary Bypass (CPB) with vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH) D] < 20 ng/mL) and normal kidney function (creatinine <1.5mg/dL). The exclusion criteria were: recent myocardial infarction, urgent CABG, non-isolated coronary surgery, redo surgery, malignant disease, presence of acute or chronic inflammatory diseases, history of vitamin D treatment within previous 6 months, or unwillingness to participate.

Intervention Following informed consent, eligible study participants were randomly assigned (by using a computer- generated random code) in a 1:1 ratio to receive either placebo or a total of 450,000 international units (IU) vitamin D3 (three 50,000 IU of vitamin D3 tablet daily for 3 days) before operation. The placebo group received three inactive medication tablets daily at the same time point. With the exception of the pharmacists, all the investigators, patients and the medical team were blinded to the group allocation.

Coronary artery bypass was done in the culprit lesions for both groups by one surgical team. The standard protocol for general anesthesia, surgical and CPB management were performed for all patients and have already been described in detail [16].

Outcome measures The primary outcome was the degree of heart apoptosis by measurement of caspase 2, 3 and 7 activity from right atrial specimen with immunohistochemistry staining, and the serum level of anti-inflammatory interleukin-10 (IL-10) and insulin- like growth factor (IGF-1), and N-terminal pro v-type Brain Natriuretic Peptide (nt-pro BNP). The biopsy from right atrial appendage was taken at the end of surgery after venous cannula removal in a nontraumatic fashion, kept into formalin and in less than 24h parafinized. Blood samples were collected at the baseline (T1), before anesthesia induction (T2), at the end of surgery after protamine reversal (T3) and the first postoperative day (T4) to measure the serum level of IGF-1, IL-10 and pro BNP. The blood samples were centrifuged at 2500 rpm for 15 min within one hour after blood sampling, and the serum was stored at -20°C until assayed.

Enzyme-linked immunosorbent assay The concentration of IL-10 was measured by a quantitative ELISA kit . The concentration of the IGF- 1 was measured by a quantitative ELISA kit .

Serum vitamin D was detected by using the high performance liquid chromatography method . The pro BNP measurement was done using a commercially available two- site chemiluminescent immunometric assay .

Immunohistochemistry studies Immunohistochemical staining was performed on 5-micrometer thick sections. The slides were incubated at 37°C for 24 hours and de-paraffinized in pre-heated xylene and rehydrated through descending grades of alcohol, washed in distilled water. Heat induced antigen retrieval was done by microwave oven with citrate buffer (pH 6.0) for anti-caspase-7 and Ethylenediamine Tetraacetic Acid; buffered solution (Tris-EDTA) (pH=8) for anti-caspase-2 and 3. endoperoxidase blocking was done by adding hydrogen peroxide on the sections. The protein block then added for 5 minutes, slides were washed in Tris-Buffered Saline (TBS). .The primary antibody as anti-caspase-2 antibody, rabbit monoclonal , anti-caspase-3 antibody, rabbit monoclonal , anti-caspase-7 antibody, and mouse monoclonal (clone 7-1-11 , abcam) antibody were added and kept for 30 minutes, washed in TBS. Mouse and Rabbit Specific horseradish peroxidase/Diaminobenzidine (HRP/DAB) immunohistochemistry (IHC) Detection Micro-polymer Kit were used and incubated for 15 minutes then washed with tris-buffered saline (TBS). Diaminobenzidine (DAB) chromogen was added and kept for 5 minutes. Slides washed in distilled water and counter stained with hematoxylin. Sections containing lymph node tissue were used as positive control. Negative control included primary antibody replaced with phosphate buffered saline (PBS). Immunostained sections were reviewed for cytoplasmic expression of anti-caspase-2, anti-caspase-3 and anti-caspase-7. The number of immune-reactive cells per High Power Field (HPF) (X 400) was counted. For this purpose at least 10 HPF were assessed and the average of positive cells was recorded.

Sample size and statistical methods The determination of the patient number (30 patients per group) was based on previous trials investigating the caspase activity in the CABG setting .

Categorical variables were reported as numbers and percentages, whereas mean± standard deviation was expressed for continuous variables. Repeated measures of analysis of variance and multiple comparisons using the Bonferroni correction (type I error correction) were applied for evaluating the change of measured inflammatory markers between the groups over time. The Kolmogorov-Smirnov test for normality was performed. Continuous variables and categorical variables were compared between groups using Student's t test (or Mann-Whitney test for those meeting abnormal distribution) and Chi-square, respectively. All the statistical analyses were performed using SPSS version 23 (SPSS, Chicago, IL, USA). A p values <0.05 was considered to be significant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: With the exception of the pharmacists, all the investigators, patients and the medical team were blinded to the group allocation.
• Primary Purpose: Prevention
• Official Title: Vitamin D Treatment Attenuates Heart Apoptosis After Coronary Artery Bypass Surgery; A Double-Blind Randomized Placebo-Controlled Clinical Trial
• Actual Study Start Date: Sep 1, 2017
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Jan 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vitamin D 35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units	Drug: Vitamin D; Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery
Placebo Comparator: control group 35 patients that will receive placebo for 3 days and each day for 3 doses	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Caspase 2 Enzyme Level [during the surgery, an average of 3 hours]

   Caspase 2 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.

2. Caspase 3 Enzyme Level, an Average of 3 Hours [during the surgery, an average of 3 hours]

   Caspase 3 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.

3. Caspase 7 Enzyme Level [during the surgery, an average of 3 hours]

   Caspase 7 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.

4. Interlukin-10 (IL-10) Serum Level [Right before the intervention(3 days before surgery)]

   The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .

5. Interleukin-10 (IL-10) Serum Level [procedure (before anesthesia induction)]

   The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .

6. Interleukin--10 (IL-10) Serum Level [at the end of surgery after protamine reversal]

   The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .

7. Interleukin (IL-10) Serum Level [the first postoperative day]

   The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .

8. Insulin Growth Factor [Right before the intervention(3 days before surgery)]

   The concentration of the IGF-1 was also measured by a quantitative ELISA kit

9. Insulin Growth Factor [procedure (before anesthesia induction)]

   The concentration of the IGF-1 was also measured by a quantitative ELISA kit

10. Insulin Growth Factor [at the end of surgery after protamine reversal]

    The concentration of the IGF-1 was also measured by a quantitative ELISA kit

11. Insulin Growth Factor [the first postoperative day]

    The concentration of the IGF-1 was also measured by a quantitative ELISA kit

Secondary Outcome Measures

1. Hemorrhage After Surgery [immediately after surgery]

   after the surgery all the hemorrhage of patients was collected by suctioning and the exact amount of bleeding has been reported.

2. Blood Units Usage [discharge 1 day]

   number of pack cell that was administered for the patient

3. Ventilator Application [discharge 1 day]

   period of time that the patient was on ventilator

4. Creatinine Level [immediately after surgery]

   The serum level of Creatinine in the patients which is a measurement of the kidney function

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Candidate for first-time elective CABG surgery for coronary artery disease (CAD)

2. Coronary artery surgery only (i.e. no valvular surgery)

3. Cardiopulmonary pump used during surgery

4. Vitamin D level below 30 ng/ml

Exclusion Criteria:

1. Renal failure or creatinine level >1.5 mg/dl

2. Previous use of vitamin D supplement

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	modarres Hospital	Tehran		Iran, Islamic Republic of

Sponsors and Collaborators

• Shahid Beheshti University of Medical Sciences

Investigators

• Principal Investigator: Erfan Tasdighi, MD, Shahid Beheshti university of medical science

Study Documents (Full-Text)

• Study Protocol - Oct 24, 2020
• Statistical Analysis Plan - Oct 24, 2020

More Information

Publications

None provided.

• Responsible Party: Erfan Tasdighi, Principle investigator, Shahid Beheshti University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT04323852
• Other Study ID Numbers: 13312; ISRCTN44896820; IRCT20180118038423N1
• First Posted: Mar 27, 2020
• Last Update Posted: Oct 19, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Erfan Tasdighi, Principle investigator, Shahid Beheshti University of Medical Sciences: Vitamin D; Cardiovascular disease; Apoptosis; Insulin-like growth factor-1; Coronary artery disease; Cardiopulmonary bypass; Interleukin-10
• Additional relevant MeSH terms: Cardiomyopathies; Vitamin D Deficiency; Inflammation; Vitamin D

Study Results

Participant Flow

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Period Title: Overall Study
STARTED	35	35
COMPLETED	35	35
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Vitamin D	Control Group	Total
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo	Total of all reporting groups
Overall Participants	35	35	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (6)	58 (9)	58.5 (7)
Sex: Female, Male (Count of Participants)
Female	8 22.9%	7 20%	15 21.4%
Male	27 77.1%	28 80%	55 78.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Iran	35 100%	35 100%	70 100%
Ejection Fraction (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	47 (10)	48 (9)	47.5 (8)
Myocardial infarction (Count of Participants)
Count of Participants [Participants]	19 54.3%	15 42.9%	34 48.6%
Erythrocyte sedimentation rate (ESR) (mm/hour) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm/hour]	13 (9)	14 (8)	13.6 (4)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27 (3)	27 (3)	27 (1)
25 (OH)D (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	12.8 (6)	12.1 (5)	12.4 (4)
Hyperlipidemia (Count of Participants)
Count of Participants [Participants]	9 25.7%	16 45.7%	25 35.7%
Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	12 34.3%	19 54.3%	31 44.3%
Hypertension (Count of Participants)
Count of Participants [Participants]	18 51.4%	22 62.9%	40 57.1%
Smokers (Count of Participants)
Count of Participants [Participants]	15 42.9%	21 60%	36 51.4%
Family history of cardiovascular disease (Count of Participants)
Count of Participants [Participants]	9 25.7%	8 22.9%	17 24.3%

Outcome Measures

1. Primary Outcome

Title	Caspase 2 Enzyme Level
Description	Caspase 2 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.
Time Frame	during the surgery, an average of 3 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [cells/ HPF]	1.3 (1.0)	2.0 (0.9)

2. Primary Outcome

Title	Caspase 3 Enzyme Level, an Average of 3 Hours
Description	Caspase 3 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.
Time Frame	during the surgery, an average of 3 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [cells/ HPF]	1.2 (0.8)	2.0 (0.8)

3. Primary Outcome

Title	Caspase 7 Enzyme Level
Description	Caspase 7 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.
Time Frame	during the surgery, an average of 3 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [cells/ HPF]	1.3 (1.0)	1.8 (1.2)

4. Primary Outcome

Title	Interlukin-10 (IL-10) Serum Level
Description	The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
Time Frame	Right before the intervention(3 days before surgery)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [pg/ml]	1.0 (0.35)	1.0 (0)

5. Primary Outcome

Title	Interleukin-10 (IL-10) Serum Level
Description	The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
Time Frame	procedure (before anesthesia induction)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [pg/ml]	4.4 (4.9)	1.0 (0)

6. Primary Outcome

Title	Interleukin--10 (IL-10) Serum Level
Description	The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
Time Frame	at the end of surgery after protamine reversal

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [pg/ml]	304.8 (85.6)	205.5 (107.4)

7. Primary Outcome

Title	Interleukin (IL-10) Serum Level
Description	The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
Time Frame	the first postoperative day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [pg/ml]	7.6 (6.5)	4.0 (6.7)

8. Primary Outcome

Title	Insulin Growth Factor
Description	The concentration of the IGF-1 was also measured by a quantitative ELISA kit
Time Frame	Right before the intervention(3 days before surgery)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [ng/mL]	86.3 (33.9)	76.5 (26.6)

9. Primary Outcome

Title	Insulin Growth Factor
Description	The concentration of the IGF-1 was also measured by a quantitative ELISA kit
Time Frame	procedure (before anesthesia induction)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [ng/mL]	109.8 (63.2)	75.0 (21.3)

10. Primary Outcome

Title	Insulin Growth Factor
Description	The concentration of the IGF-1 was also measured by a quantitative ELISA kit
Time Frame	at the end of surgery after protamine reversal

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [ng/mL]	142.0 (67.1)	82.1 (35.9)

11. Primary Outcome

Title	Insulin Growth Factor
Description	The concentration of the IGF-1 was also measured by a quantitative ELISA kit
Time Frame	the first postoperative day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [ng/mL]	108.6 (61.2)	69.4 (35.4)

12. Secondary Outcome

Title	Hemorrhage After Surgery
Description	after the surgery all the hemorrhage of patients was collected by suctioning and the exact amount of bleeding has been reported.
Time Frame	immediately after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [cc]	360.7 (237.7)	404.4 (245.9)

13. Secondary Outcome

Title	Blood Units Usage
Description	number of pack cell that was administered for the patient
Time Frame	discharge 1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [units]	0.5 (0.7)	0.8 (0.9)

14. Secondary Outcome

Title	Ventilator Application
Description	period of time that the patient was on ventilator
Time Frame	discharge 1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [hr]	6.8 (2.3)	8.3 (4.4)

15. Secondary Outcome

Title	Creatinine Level
Description	The serum level of Creatinine in the patients which is a measurement of the kidney function
Time Frame	immediately after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D	Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery	35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
Measure Participants	35	35
Mean (Standard Deviation) [mg/dl]	.8 (.05)	.9 (.04)

Adverse Events

Time Frame	2 weeks
Arm/Group Title	Vitamin D		Control Group
Arm/Group Description	35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units Vitamin D: Participants undergoing coronary artery bypass graft (CABG) surgery are randomly allocated to group A (intervention), who receive 3 doses of vitamin D (50000 U) a day for 3 days before surgery		35 patients that will receive placebo for 3 days and each day for 3 doses Placebo: Placebo
All Cause Mortality
	Vitamin D		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Serious Adverse Events
	Vitamin D		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/35 (11.4%)		5/35 (14.3%)
Cardiac disorders
heart attack	1/35 (2.9%)	1	2/35 (5.7%)	2
Gastrointestinal disorders
gastrointestinal bleeding	1/35 (2.9%)	2	1/35 (2.9%)	2
Nervous system disorders
brain stroke	2/35 (5.7%)	3	2/35 (5.7%)	2
Other (Not Including Serious) Adverse Events
	Vitamin D		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/35 (20%)		7/35 (20%)
Immune system disorders
infection	5/35 (14.3%)	6	6/35 (17.1%)	7
Vascular disorders
DVT	2/35 (5.7%)	3	1/35 (2.9%)	2

Limitations/Caveats

Although this single-center study had a relatively small sample size and was limited to cardiac surgery patients, the study design was RCT with homogenous patients.

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.