Therapeutic Zinc in Childhood Pneumonia

Pneumonia Clinical Trial

Official title:

Efficacy of Zinc as Adjuvant Therapy in the Treatment of Severe Pneumonia in Nepalese Children at the Kanti Children's Hospital

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00252304
• Other study ID #: INCO-CT-2004-003740-2
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: November 10, 2005
• Last updated: October 2, 2009
• Start date: January 2006
• Est. completion date: July 2008

Study information

• Verified date: October 2009
• Source: Centre For International Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway:National Committee for Medical and Health Research Ethics
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to assess whether zinc given as adjuvant therapy to standard antibiotic treatment in children hospitalized for severe pneumonia reduces the duration of the severe illness and risk of treatment failure. A randomized double blind placebo controlled clinical trial will be conducted at the Kanti Hospital.

Description:

Nepal has an under-five mortality rate of 91/1000 live births. Pneumonia, one of the major killers accounts for the death of 25,000 - 35,000 Nepalese children every year. It is estimated that, on an average, of 1000 children <5 years of age that visit health facilities, 90 have pneumonia of which 4.2 have severe pneumonia. At the Kanti Children's Hospital, respiratory diseases are the most frequent reason for admission and the second most frequent cause of child death Zinc, an important micronutrient, is crucial for the normal function of the immune system as well as the integrity of the respiratory epithelium. Zinc deficiency is associated with an increased incidence and severity of diarrhea and respiratory tract infections. The preventive effect of zinc on diarrheal and respiratory illness has been well documented.

Early in an infection zinc is shifted into the liver from the plasma, bone, skin and intestines. For a child with initial low zinc levels, even relatively trivial infections may cause entry into the vicious cycle of reduced plasma zinc and increased infection severity. Administration of zinc during the acute illness may help in reducing the severity of illness.

The therapeutic effect of zinc in acute diarrhea has been well documented. In a study conducted at Bhaktapur, Nepal, in children 6 to 36 months of age, supplementation with zinc was found to be highly effective in the treatment of acute diarrhea.

The Kanti Children's Hospital in Kathmandu serves as a general and referral hospital for children from all parts of the country. Approximately 25% of all admissions to this hospital are due to pneumonia. Being the only well recognized children's hospital, there is always a constraint for available beds for children presenting with pneumonia. Zinc as an adjuvant to standard treatment of pneumonia with antimicrobials was found to hasten recovery from severe pneumonia in children less than 2 years of age in Bangladesh . If we were to conduct a similar study and prove that zinc does in fact help to shorten the duration of illness in children with severe pneumonia, it would go a long way in contributing to improve case management.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 641
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Months to 35 Months

Eligibility

Inclusion Criteria:

• Children aged 2- 35 months with a history of cough (duration <14days) and difficult breathing of </= 72hours' duration, with lower chest indrawing.

• Availability of informed consent.

Exclusion Criteria:

• Children with severe wasting (<70% NCHS median weight for height)

• Severe anemia (hemoglobin <7 gm/dl.)

• Presence of heart disease with or without signs of cardiac failure.

• Child with a chronic cough (lasting for =14 days)

• Documented tuberculosis with ongoing treatment.

• Associated other severe diseases that require special care or surgical intervention.

• Children with concomitant diarrhea with some/severe dehydration

• Children with a history of recurrent wheezing

• Children enrolled in the study within the last 6 months of this visit

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia

Intervention

Drug:
• Zinc (zinc sulphate)
Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months
• Placebo
Placebo

Locations

Country	Name	City	State
Nepal	Kanti Children Hospital	Kathmandu

Sponsors (6)

Lead Sponsor	Collaborator
Centre For International Health	All India Institute of Medical Sciences, New Delhi, Institut de Recherche pour le Developpement, Society for Applied Studies, Statens Serum Institut, Tribhuvan University, Nepal

Country where clinical trial is conducted

Nepal, 

References & Publications (13)

Bahl R, Bhandari N, Hambidge KM, Bhan MK. Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting. Am J Clin Nutr. 1998 Aug;68(2 Suppl):414S-417S. — View Citation

Beisel WR. Zinc metabolism in infection. In: Brewer GJ, Prasad AS, eds. Zinc metabolism: current aspects in health and disease. New York: Alan R Liss, 1977: 973-977

Bhandari N, Bahl R, Taneja S, Strand T, Mølbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Substantial reduction in severe diarrheal morbidity by daily zinc supplementation in young north Indian children. Pediatrics. 2002 Jun;109(6):e86. — View Citation

Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000 Dec;72(6):1516-22. — View Citation

Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. J Pediatr. 1999 Dec;135(6):689-97. — View Citation

Brooks WA, Yunus M, Santosham M, Wahed MA, Nahar K, Yeasmin S, Black RE. Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Lancet. 2004 May 22;363(9422):1683-8. — View Citation

Brown KH. Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries. Am J Clin Nutr. 1998 Aug;68(2 Suppl):425S-429S. Review. — View Citation

Cousins RJ, Leinart AS. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J. 1988 Oct;2(13):2884-90. — View Citation

Nepal Demographic and Health Survey, 2001

Nepal Ministry of Health, Department of Health Services Annual Report 2000- 2001, Kathmandu

Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug;68(2 Suppl):447S-463S. Review. — View Citation

Strand TA, Chandyo RK, Bahl R, Sharma PR, Adhikari RK, Bhandari N, Ulvik RJ, Mølbak K, Bhan MK, Sommerfelt H. Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children. Pediatrics. 2002 May;109(5):898-903. — View Citation

Strand TA, Hollingshead SK, Julshamn K, Briles DE, Blomberg B, Sommerfelt H. Effects of zinc deficiency and pneumococcal surface protein a immunization on zinc status and the risk of severe infection in mice. Infect Immun. 2003 Apr;71(4):2009-13. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to cessation of severe pneumonia		Within 2 weeks after enrollment	No
Primary	The period starting from enrolment to the beginning of a 24-hour consecutive period of absence of lower chest indrawing, of hypoxia and of any danger signs.		Recovery from pneumonia within 2 weeks	No