Vitamin D Supplementation Effect In Children With Pulmonary Tuberculosis Treatment
Condition: Tuberculosis, Pulmonary
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional

Summary: 
      This study aims to evaluate the vitamin D supplementation effect to improve clinical outcomes
      in children with pulmonary tuberculosis treatment. This randomized, double-blind control
      trial with a cohort design was conducted in West Borneo from December 2020 - July 2021. A
      Total 84 patients met the inclusion criteria; aged 6 to 18 years old, newly diagnosed with
      pulmonary tuberculosis with vitamin D insufficiency. Only 80 patients completed the six
      months follow-up. The intervention was 1,000 IU vitamin D or placebo for six months
      treatment. Comparison of clinical conditions and nutritional status are analyzed
      statistically.
    

Detailed description: 
      This randomized, double-blind control trial with a cohort design was conducted in Bethesda
      Hospital West Borneo from December 2020 - May 2021. The inclusion criteria were children
      between 6 to 18 years old, newly diagnosed with pulmonary tuberculosis with vitamin D
      insufficiency. Diagnosis of the tuberculosis case was based on The Indonesian Pediatric
      Tuberculosis Scoring System. It consists of history taking and laboratory findings that
      support tuberculosis common symptoms such as household contact, prolonged fever more than two
      weeks, non-remitting cough more than three weeks, and decrease body weight, and lymph node
      enlargement; laboratory findings include Tuberculin Skin Test (TST) and chest X-ray (CXR).
      Scoring ranges from 0 to 3 for each variable with a total score of more than six is
      considered as tuberculosis diagnosis. Patients also collect the sputum for gram staining and
      Xpert MTB/RIF examination. The isolation of Mycobacterium tuberculosis was not done in this
      study because of limited resources.

      Subject selection was determined based on consecutive sampling, namely the order of patients
      who came to the clinic until the minimum sample size (84 subjects) met the inclusion
      criteria. The investigators excluded children with a history of liver or kidney
      abnormalities, immunocompromised, and already received vitamin D supplementation. After
      obtaining written consent, all subjects had their blood specimens drawn 3cc from the brachial
      vein to measure alanine transaminase (ALT), alkaline phosphatase (ALP), serum active
      25-hydroxyvitamin D using the ELISA method. Vitamin D is categorized as deficiency if serum
      25-hydroxyvitamin D is below 20ng/mL, insufficiency between 20-30ng/mL, and normal levels
      above 30ng/mL. In this study, the 95% confidence level (Zα = 1.65 one-sided test) and 80%
      power test (Zß = 0.84) were selected. The calculation of the sample size above obtained n =
      35 people for each group. The total study subjects were added by 20% of the minimum number of
      samples to compensate for loss-to-follow-up, so the total sample was 84, consisting of 42
      patients in the intervention group and 42 patients in the placebo group.

      For each subject, the following data were entered into the study database demographic data (
      name, age, sex), signs and symptoms (fever, cough), Tuberculin Skin Test (TST), Chest X-Ray,
      and also GeneXpert for Mycobacterium tuberculosis from gastric lavage or sputum induction,
      liver function test and 25-hydroxyvitamin D level. All results were recorded in a study
      database following international standards to protect the privacy and personal information.

      Subjects were randomly assigned to receive either a 1000IU vitamin D supplement dose or a
      placebo with an allocation ratio of one to one. Before starting recruitment, the project
      manager prepared 84 packs of study preparation - 42 packs of the active study drug and 42
      packs of a placebo, then generated a randomization sequence using a computer program
      assigning the terms active or placebo to numbers 1 to 84. The packs were then assigned a
      randomized number according to this computer-generated randomization sequence.

      At recruitment, study staff enrolled patients consecutively according to the order of arrival
      of patients from number 1 to 84. Study staff who assigned patients to active drugs or placebo
      did not know the following assignment in the sequence because they did not have access to the
      study code. Treatment allocations were hidden from patients and research staff. Those who
      analyzed the data were not covered for group assignments. Monitoring of subjects medication
      adherence and daily symptoms conducted by using a checklist table filled out by the patient's
      parents and confirmed check by the researcher during the patient follow-up schedule to the
      clinic.

      All subjects received antimicrobial treatment for tuberculosis drugs in the form of a
      fixed-dose combination. Patients were reviewed monthly after starting antimicrobial
      treatment; body weight and height were measured at each time point. After the intensive phase
      of antimicrobial treatment, patients were monitored monthly. A repeated vitamin D level by
      ELISA and liver function test were done six months after starting the antimicrobial
      treatment.
    

Intervention name(s): Vitamin D; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Subjects were assigned to receive a 1000IU vitamin D supplement dose; Subject were assigned to receive a placebo
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care