Vitamin D Supplementation for Severe Pneumonia in Under-five Children: A Double Blind, Randomized Placebo Controlled Trial
试验速览
- 阶段
- Phase 3 4
- 状态
- 已完成
- 入组人数
- 324
- 试验地点
- 1
- 主要终点
- 1. Time to resolution of severe pneumonia: The duration from the enrolment till the chest indrawing is no longer present, and continue to be absent for next 24 hours.
研究概览
简要总结
**Objective:**To evaluate the efficacy of single oral mega-dose of Vitamin D3 for treatment and prevention of pneumonia in under-five children.
**Design:**Randomized, double blind, placebo-controlled trial.
**Setting:**Tertiary-care hospital.
**Participants:**324 children (of 980 assessed) between 6 mo-5 y age (median (IQR): 12 (7,19.8) mo) with WHO-defined severe pneumonia. Of these, 126 (39%) were vitamin D deficient (serum 25(OH)D <12 ng/mL).
**Intervention:**100,000 IU of oral cholecalciferol (n= 162) or placebo (n= 162) in single dose, administered at enrolment. Outcome variables: Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness.
**Outcome variables:**Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness.
**Results:**Median (95% CI) time for resolution of severe pneumonia was 30 (29, 31) h in the vitamin D group as compared to 31 (29,33) h in the placebo group [adjusted hazard ratio (95% CI): 1.39 (1.11, 1.76); P = 0.005]. The risk of recurrence of pneumonia in next 6 months was comparable in the two groups [placebo: 36/158 (22.8%); vitamin D: 39/156 (25%); RR (95% CI): 1.13 (0.67,1.90); P 0.69]. Proportion of vitamin D deficient children declined from 38% to 4% in the supplementation group, and from 41% to 33% in the placebo group, two weeks after supplementation. There was no significant effect of vitamin D supplementation on serum levels of cathelicidin, IgA and IgG. The time taken for complete recovery from pneumonia, duration of hospitalization, and fever clearance time were comparable for the two groups. No adverse event was noted related to the intervention.
**Conclusion:**There is no robust evidence of a definite biological benefit, either for therapy or prevention, to suggest a routine megadose supplement of vitamin D3 for under-five children with severe pneumonia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 6.00 Month(s) 至 5.00 Year(s)（—）
- 性别
- All
入选标准
- •Children with severe pneumonia.
排除标准
- •Exclusion criteria 1.Children who have received vitamin D or calcium supplements within last 4 weeks, as ascertained on verbal enquiry (ingestion of oral formulation as sachets/granules or syrups or tablets).
- •Where ever possible the parents will be asked to show the prescription of the physician or empty bottles, sachets or tablets consumed by the child.
- •2.Children with clinical features of rickets 3.Children with severe malnutrition (weight for height less than -3 SD of WHO standards or presence of bipedal edema) 4.Known asthmatics 5.Those with complicated pneumonia (lung abscess, pleural effusion, empyema) or illness severe enough to require ventilation.
- •6.Those suffering from any chronic respiratory disease including respiratory tract malformations and chest wall deformities, heart disease (congenital/acquired), renal or hepatic insufficiency, neurological illness resulting in abnormalities of muscle tone/power 7.Those known to have hypercalcemia or allergy to vitamin D 8.Children immunized with pneumococcal/flu vaccine 9.Known immunodeficiency.
结局指标
主要结局
1. Time to resolution of severe pneumonia: The duration from the enrolment till the chest indrawing is no longer present, and continue to be absent for next 24 hours.
时间窗: 1. 7 days | 2. 6 months
2. Proportion of children having a repeat episode of pneumonia in next six months.
时间窗: 1. 7 days | 2. 6 months
次要结局
- Duration of hospitalization(At discharge)
- Change in serum levels of cathelicidin(72 hours)
- Time to complete recovery from pneumonia (Normalization of RR)(7 days)
- Fever clearance time(7 days)
- Failure rate (Non-response after 48 hours of antibiotic therapy)(48 hours)
- Time to start oral feeds(7 days)
- Change in serum levels of immunoglobulins (Ig A, IgG, IgM)(72 hours)