| Methods |
Study design: randomised, double‐blind, placebo‐controlled trial
Study duration: 29 months |
| Participants |
Inclusion criteria
Setting: hospital inpatients department Country: India Health condition: children aged 6 months to 5 years hospitalised with severe pneumonia Number: N = 324; treatment (162); control (162) -
Age (mean, SD)
Sex (m): treatment: 69.7%; control: 69.7% Other information: the prevalence of moderate malnutrition as per WHO definition was 21.3%. The prevalence of anaemia (Hb < 11 g/dL) was 82.4%, hypocalcaemia was 55.9%, hypophosphataemia was 31.4%. Vitamin D deficiency was present in 37.6% of children in the vitamin D group and 40.1% of children in the placebo group. Wheezing was present in 84.6% of children in the vitamin D group and 78.4% of children in the control group.
Exclusion criteria
Children with rickets, severe acute malnutrition, asthma, hypertension, complicated pneumonia or illness severe enough to require ventilation, chronic respiratory disease, heart disease, renal or hepatic insufficiency, neurological illness, immunodeficiency, received vitamin D or calcium supplements within 4 weeks prior to enrolment, and those with hypercalcaemia or allergy to vitamin D, or immunised with pneumococcal/flu vaccine were excluded.
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| Interventions |
Treatment group
Intervention: vitamin D₃ Dose, duration, frequency: oral vitamin D₃ was given as a single dose of 100,000 IU on day of enrolment
Control group
Intervention: placebo not described Dose, duration, frequency: oral placebo was given as a single dose on day of enrolment
Co‐interventions
Antibiotics were administered as per the IAP 2006 guidelines (< 3 months: cefotaxime/ceftriaxone ± gentamicin/amikacin as first line, and co‐amoxyclav + gentamicin/amikacin as second line; 3 months to 5 years: ampicillin/chloramphenicol or ampicillin + chloramphenicol or co‐amoxyclav as first line, and co‐amoxyclav or cefotaxime/ceftriaxone as second line. In staphylococcal infection, cloxacillin as first line and vancomycin/teicoplanin as second line was added to any of the above combinations in the respective age groups).
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| Outcomes |
Primary
Time to resolution of severe pneumonia (the duration from enrolment until the chest indrawing was no longer present, and continued to be absent for next 24 hours) The proportion of children having a recurrence of pneumonia in next 6 months
Secondary
Change in the serum level of 25(OH)‐D and PTH after 2 weeks and 3 months of therapy Change in serum level of cathelicidin and immunoglobulins (IgA, IgG, IgM) after 2 weeks of therapy Duration of hospitalisation Time to complete recovery from pneumonia (normalisation of respiratory rate) Fever clearance time Incidence rate of pneumonia during follow‐up
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| Notes |
Funding source: not funded by any funding agency
Other: blood culture was positive in 8.6% (Staphylococcus aureus isolated in 8.3%), and 90.1% of children abnormal chest x‐ray in the form of consolidation, bilateral patchy opacities, and hyperinflation or minor infiltrates.
Contact with study authors: no |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Computer randomisation |
| Allocation concealment (selection bias) |
Low risk |
Sealed envelopes were used. |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Blinding of participants and caretaker was ensured and unlikely that the blinding could have been broken, as both the intervention and placebo looked alike in terms of appearance, taste, and colour. |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
The code key was opened only after the intervention, data collection, follow‐up, and tabulation were completed. |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
4.63% (15/324) children lost to follow‐up |
| Selective reporting (reporting bias) |
Low risk |
The trial was registered. |
| Other bias |
Low risk |
No other known risks of bias |
