Trial Outcomes & Findings for A Study to Evaluate the Effect of Vitamin D on PFS in Indolent Non-Hodgkin's Lymphoma (NCT NCT03078855)

Last Updated: 2024-09-04

Results Overview

Event free survival (EFS) was defined as the time from randomization to lack of response at week 13, initiation of a new treatment, disease progression defined by Lugano criteria, or death, right-censored by time of last follow-up. Per Lugano criteria, progression is defined as a new FDG-avid lesion or an increase in intensity from baseline, an increase by \>= 50% in lesion diameters, a new lymph node \> 1.5 cm in any axis or a new extranodal site \> 1.0 cm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

211 participants

Primary outcome timeframe

3 years

Results posted on

2024-09-04

Participant Flow

Participants were enrolled at 7 US academic medical centers between September 2017 and March 2022.

Participant milestones

Participant milestones
Measure	Vitamin D Plus Rituximab Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment. Vitamin D: vitamin D3 2,000 IU daily Rituximab: Administered weekly x 4	Placebo Plus Rituximab Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment. Placebo: methylcellulose Rituximab: Administered weekly x 4
Overall Study STARTED	139	72
Overall Study COMPLETED	53	32
Overall Study NOT COMPLETED	86	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Vitamin D Plus Rituximab Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment. Vitamin D: vitamin D3 2,000 IU daily Rituximab: Administered weekly x 4	Placebo Plus Rituximab Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment. Placebo: methylcellulose Rituximab: Administered weekly x 4
Overall Study Lack of Efficacy	62	31
Overall Study Death	1	0
Overall Study Withdrawal by Subject	12	6
Overall Study Physician Decision	3	2
Overall Study Second Malignancy	4	0
Overall Study Ineligible	2	0
Overall Study Withdrew before day 1 treatment	2	1

Baseline Characteristics

A Study to Evaluate the Effect of Vitamin D on PFS in Indolent Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vitamin D Plus Rituximab n=135 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU, was taken orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment.	Placebo Plus Rituximab n=71 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo was taken orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment.	Total n=206 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	80 Participants n=5 Participants	36 Participants n=7 Participants	116 Participants n=5 Participants
Age, Categorical >=65 years	55 Participants n=5 Participants	35 Participants n=7 Participants	90 Participants n=5 Participants
Age, Continuous	62 years n=5 Participants	64 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	78 Participants n=5 Participants	40 Participants n=7 Participants	118 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	31 Participants n=7 Participants	88 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	123 Participants n=5 Participants	63 Participants n=7 Participants	186 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	120 Participants n=5 Participants	62 Participants n=7 Participants	182 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	135 participants n=5 Participants	71 participants n=7 Participants	206 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 years

Population: The analysis population included randomized and eligible participants that received at least one dose of vitamin D or placebo.

Outcome measures

Outcome measures
Measure	Vitamin D Plus Rituximab n=135 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU, was taken orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment.	Placebo Plus Rituximab n=71 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo was taken orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment.
Event Free Survival	47.7 Percentage of Participants Interval 39.0 to 58.4	49.5 Percentage of Participants Interval 37.6 to 65.0

SECONDARY outcome

Timeframe: Participants were followed for survival beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months.

Population: The analysis population included randomized and eligible participants that received at least one dose of vitamin D or placebo.

Number of participants who died from any cause between day 1 of treatment and the time of last follow-up.

Outcome measures

Outcome measures
Measure	Vitamin D Plus Rituximab n=135 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU, was taken orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment.	Placebo Plus Rituximab n=71 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo was taken orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment.
All-Cause Mortality	4 Participants	3 Participants

SECONDARY outcome

Timeframe: 13 Weeks from the start of treatment

Population: The analysis population included randomized and eligible participants that received at least one dose of vitamin D or placebo and were evaluated for treatment response at 13 weeks.

Participants had imaging performed at week 13 to assess response to treatment. A response was defined as partial (PR) or complete response (CR) according to Lugano criteria. Per Lugano criteria for target lesions: PR includes reduced metabolic uptake or a ≥ 50% decrease in the sum of the products of the diameters compared to baseline. CR includes metabolic score of 1, 2 or 3 (out of 5) with or without residual mass or regression of target lesions to ≤ 1.5 cm in the longest dimension.

Outcome measures

Outcome measures
Measure	Vitamin D Plus Rituximab n=135 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU, was taken orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment.	Placebo Plus Rituximab n=70 Participants Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo was taken orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment.
Number of Participants With Treatment Response at 13 Weeks	113 Participants	59 Participants

Adverse Events

Vitamin D Plus Rituximab

Serious events: 16 serious events

Other events: 111 other events

Deaths: 4 deaths

Placebo Plus Rituximab

Serious events: 9 serious events

Other events: 54 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Michael Brady, PhD

University of Rochester

Phone: 585-275-5830

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Vitamin D Plus Rituximab n=135 participants at risk Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU, was taken orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment.	Placebo Plus Rituximab n=71 participants at risk Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo was taken orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment.
General disorders Chills	5.9% 8/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	1.4% 1/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
General disorders Fatigue	28.9% 39/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	26.8% 19/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
General disorders Fever	5.2% 7/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	1.4% 1/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
General disorders Infusion related reaction	35.6% 48/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	31.0% 22/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
General disorders Injection site reaction	10.4% 14/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	11.3% 8/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Gastrointestinal disorders Abdominal pain	8.1% 11/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	1.4% 1/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Gastrointestinal disorders Constipation	7.4% 10/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Gastrointestinal disorders Diarrhea	5.9% 8/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Gastrointestinal disorders Nausea	7.4% 10/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	8.5% 6/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Infections and infestations Other - COVID19	8.9% 12/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	12.7% 9/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Infections and infestations Upper respiratory infection	6.7% 9/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	11.3% 8/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Musculoskeletal and connective tissue disorders Arthralgia	8.9% 12/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Musculoskeletal and connective tissue disorders Back pain	10.4% 14/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	8.5% 6/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 8/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Musculoskeletal and connective tissue disorders Myalgia	4.4% 6/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Nervous system disorders Dizziness	5.2% 7/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	1.4% 1/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Nervous system disorders Headache	13.3% 18/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	7.0% 5/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Respiratory, thoracic and mediastinal disorders Cough	8.1% 11/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.2% 7/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Skin and subcutaneous tissue disorders Pruritus	5.2% 7/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Skin and subcutaneous tissue disorders Rash maculo-papular	4.4% 6/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	5.6% 4/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.
Vascular disorders Hypertension	10.4% 14/135 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.	7.0% 5/71 • Adverse events and serious adverse events were evaluated beginning on day 1 of treatment through 30 days after the last dose of vitamin D or placebo, up to 37 months. All-cause mortality was evaluated beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months. Adverse events were collected through chart review and participant solicitation.