Zinc deficiency is a prevalent condition of young children in developing countries and is associated with decreased immunocompetence (the ability of a body to respond to pathogenic organisms/tissue damage) and increased rates of serious infectious diseases including acute lower respiratory tract infections. Studies have indicated evidence for a protective relationship between zinc and childhood infections. The primary objective of this study is to determine whether oral zinc supplementation plus standard antibiotics significantly alters the duration of required hospitalization in children aged 6 months to 36 months, who are hospitalized with radiologically confirmed acute pneumonia. Half of the subjects will receive daily oral supplements of elemental zinc and the other half will receive placebo tablets (inactive substance) that are identical in appearance and taste. The study duration will be 16 to 18 months. The duration for each subject will be approximately 6-8 weeks.

Condition	Intervention
Respiratory Infections, Acute	Drug: Zinc

Further Study Details: 

Expected Total Enrollment:  600

This is a 2-arm, randomized, double-blinded, placebo-controlled trial of zinc adjuvant therapy. Approximately 600 children aged 6 months to 36 months, who are admitted with a primary clinical diagnosis of acute severe pneumonia, will be randomized to receive zinc at a daily dose of 25 mg (12.5 mg twice daily) or placebo twice daily from the time of initial presentation to the hospital to the time of hospital discharge. All participants will receive antibiotics for a duration of 14 days and will receive a single dose of vitamin A, and supportive care as deemed appropriate according to the standards of care as practiced at MNH in accordance with the Recommendations of Ministry of Health, Tanzania. All patients will have a final clinical evaluation at 6 weeks after hospital discharge. Study drug solution will consist of either zinc or placebo, and both will be identical in taste and appearance.

Ages Eligible for Study:  6 Months   -   36 Months,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Age 6 months to 36 months inclusive.
2. A primary clinical diagnosis of acute pneumonia, which consists of a child presenting with cough or difficulty breathing with the following features: a)Tachypnea: Respiratory rate >= 50 breaths per minute for children aged 6 months up to 12 months and >= 40 breaths per minute for children aged 12 months to 36 months. b)Fever: Temperature >= 37.5ºC with an axillary thermometer. c)Any one of the following signs: Flaring of alae nasi, visible indrawing of the lower chest wall muscles on inspiration, central cyanosis, inability to drink, lethargy, or crepitations, i.e. short crackling noises heard during the inspiratory phase of respiration.
3. Parent/caregiver willing to give informed consent and to allow HIV testing of their child.
4. Child able to take study regimen (zinc supplement/placebo).
5. Parents/caregivers willing to comply with a follow-up study visit.
6. Child is anticipated to survive the episode of pneumonia and has no other serious concomitant medical condition that would affect their ability to survive the acute episode of pneumonia.
7. Chest x-ray abnormalities consistent with an inflammatory process such as distinctly confined dense abnormality or large pleural effusion (i.e., pneumonia or lower respiratory tract), not just any change such as pulmonary edema.

Exclusion Criteria:

1. Presence of severe malnutrition according to Wellcome Classification (marasmus, marasmic-kwashiorkor, and kwashiorkor), which requires microniutrient supplementation including zinc or any other sign of severe malnutrition (see Table 1 below).
2. Prior known or current diagnosis of full blown AIDS meeting WHO clinical case definition (Appendix III). Children who are only HIV-positive and have acute pneumonia will not be excluded from the study.
3. Subjects with active tuberculosis.
4. Subjects with active measles.
5. Subjects with known or suspected signs of systemic illness (e.g. sepsis, acute meningitis, haemodynamic instability).
6. Subjects with diarrhea defined as passage of 3 or more loose or watery stools in the past 24 hours.
7. Subjects for which the number of days of illness prior to admission is greater than 3 days.
8. Subjects with known allergy to any of the antibiotics used in the study, i.e. Chloramphenicol, Ampicillin, Cloxacillin, Gentamicin and Ceftriaxone.
9. Known intolerance or allergy to zinc or zinc-containing products.
10. Subjects presently receiving zinc supplementation.

Table 1 Wellcome classification of malnutrition:

Nutritional status Body weight Oedema (% of standard*)

Normal 100-80

- Underweight 80-60 - Marasmus <60 - Kwashiokor 80-60 + Marasmic-kwashiokor <60 +

• 50th centile of Harvard Standard. Courtesy of Wellcome Trust Working Party. Lancet, 1970; ii: 302

Please refer to this study by ClinicalTrials.gov identifier  NCT00133432

Maulidi Fataki      (255) 222-8434 x06 

Tanzania
      Muhimbili University, College of Health Sciences, DAR ES SALAAM,  Tanzania

Study ID Numbers:  03-179
Last Updated:  August 22, 2005
Record first received:  August 19, 2005
ClinicalTrials.gov Identifier:  NCT00133432
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23