Clinical Trial: CHIZAP

This study is currently recruiting patients.
Verified by Centre For International Health September 2005

Sponsors and Collaborators: Centre For International Health
Tribuhwan University, Institute of Medicine, Department of Child Health, Nepal
Department of Epidemiology Research, Statens Serum Institut, Denmark
Centre for International Health, University of Bergen, Norway
AIIMS, ICMR Advanced Centre for Diarrheal disease research, New Delhi, India
IRD, Epidemiologie et Prevention, Montpelier, France
Society for Applied Studies, Department of Pediatrics, Kolkata, India
Information provided by: Centre For International Health
ClinicalTrials.gov Identifier: NCT00148733

Purpose

The aim of the study described is to measure the degree with which zinc given as adjunct therapy to standard antibiotic treatment during childhood pneumonia reduces the risk of treatment failure and the duration of the illness.
Condition Intervention Phase
Pneumonia
 Drug: Zinc
Phase II
Phase III

MedlinePlus related topics:  Pneumonia

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Official Title: Community- and Health Facility-Based Intervention with Zinc as Adjuvant Therapy for Pneumonia to Enhance Child Health and Nutrition

Further Study Details: 
Primary Outcomes: Risk of treatment failure and the duration of illness. For those with severe pneumonia: length of hospital stay.; Non-injury clinic visits and hospital admissions after treatment has been initiated.; Active and passive morbidity surveillance for six months after the 14-day supplementation period is completed. Difference in growth and thymic size between the treatment groups measured at three and six months after the zinc supplementation.; Adverse effects
Secondary Outcomes: Whether the following are modifiers for the above-mentioned effect of zinc given during pneumonia.; i. severe inflammation, reflected in: high fever and/or elevated plasma C-reactive protein (CRP) concentration; ii. breast feeding status and age categories; iii. categories of nutritional status; iv. viral etiology
Expected Total Enrollment:  2700

Study start: January 2004;  Expected completion: May 2007
Last follow-up: December 2006;  Data entry closure: January 2007

Hypothesis: Zinc deficiency is a major public health problem in developing counties. Poor zinc status is associated with stunted growth and reduced resistance to infections. Several in vitro experiments and in vivo studies in animals and humans have demonstrated detrimental effects of zinc depletion on almost all facets of the immune system. The epithelial linings in the gut and in the respiratory tract are important for the resistance to infections and continuous cell division is required for proper function of these barriers. Zinc is crucial for cellular division and for the maintenance of organs with cells with a rapid turnover, including epithelial cells. Clinical trials in children in developing countries have demonstrated improved growth and reduced prevalence of diarrhea and respiratory tract infections following zinc supplementation. Furthermore, zinc has a well-documented therapeutic effect when given during acute or persistent diarrhea. The effect of zinc may be explained by correction of a deficiency state and/or by a pharmacological, as yet poorly described, action.

Due to the promising results from previous studies, WHO are now supporting large clinical trials in Nepal, India and Tanzania to assess whether routine zinc supplementation reduces mortality in early childhood. If the results of these trials show a mortality reduction, routine zinc supplementation or zinc dense foods may be promoted. However, while the first approach is logistically difficult and expensive, the second approach is difficult because zinc dense foods and foods with low phytic acid content are expensive and not readily available. Moreover, both approaches may be perceived to be incompatible with the current breast-feeding recommendations for the youngest children in most developing countries.

There is limited information on zinc as adjunct therapy for pneumonia. A recent hospital-based study in young children with severe pneumonia, showed that the zinc group had a faster recovery, resulting in a shortening of stay in hospital of one day. However, this study was small and no community based study has been conducted so far. Whether zinc has an effect during respiratory infections has to be assessed in studies with larger sample sizes in children with less severe disease and should be repeated in children with more severe disease. Short-term zinc administration during infections may become an alternative or an addition to long-term supplementation or promotion of zinc dense foods. Furthermore, therapeutic administration of zinc will not interfere with the current breast-feeding recommendations.

Hypothesis: Zinc as adjunct therapy for pneumonia may lead to faster recovery. Furthermore, long-term beneficial effects may include improved immuno-nutritional status measured by thymus size, less morbidity and improved growth.

Comparison: Duration of illness, risk of treatment failure, for those with severe pneumonia: length of hospital stay. Number of non-injury clinic visits and hospitalizations during the intervention with Zinc and an in a 6 month period after enrolment. Growth assessed by anthropometry and thymus size assessed by ultrasonography. Explore the efficacy of zinc in etiology-sub groups including those defined by nutritional status, inflammation, fever, gender, breastfeeding status and viral etiology.

Eligibility

Ages Eligible for Study:  2 Months   -   3 Years,  Genders Eligible for Study:  Both
Criteria

Inclusion Criteria:

Pneumonia: Child presenting with cough or difficult breathing and elevated respiratory rate. Severe pneumonia: Child presenting with cough or difficult breathing and chest indrawing , but without any of the following danger signs: Not able to drink/breastfeed, vomit everything, has had convulsions, is lethargic or unconscious.

Must be able to take Zinc

Exclusion Criteria:

The child requires special care for other severe illness than pneumonia Severe malnutrition defined as being < 70% NCHS median weight for height Presence of congenital heart disease Documented tuberculosis Any antibiotic treatment during the last 48 hours The child was enrolled less than 6 months ago Presence of dysentery Cough for more than 14 days

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier  NCT00148733

Tor A Strand, MD PhD      00 47 55 974 980    Tor.Strand@cih.uib.no
Halvor Sommerfelt, MD PhD      00 47 55 974 980    halvor.sommerfelt@cih.uib.no

Nepal
      Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan, Bhaktapur,  P.O.Box 40,  Nepal; Recruiting
Shyam Dhaubhadel  00977-1-985104    smh@healthnet.org.np 
Janani P Mool  00977-1-6612945 
Suddha Basnet, MD,  Sub-Investigator
Ram K Chandyo, MD MPhil,  Sub-Investigator
Maria Mathisen, MD,  Sub-Investigator
Prakash S Shrestha, MD Professor,  Principal Investigator
Valentiner-Branth Palle, MD PhD,  Principal Investigator

Study chairs or principal investigators

Tor A Strand, MD PhD,  Study Director,  Centre for International Health, University of Bergen, 5021 Bergen, Norway   
Halvor Sommerfelt, MD PhD,  Study Chair,  Centre for International Health, University of Bergen, 5021 Bergen, Norway   
Prakash S Shrestha, MD Professor,  Study Director,  Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj   
Ramesh K Adhikari, MD Dean,  Study Chair,  Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj   
Palle Valentiner-Branth, MD PhD,  Principal Investigator,  Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark   

More Information

Publications

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.

Bates CJ, Prentice A. Breast milk as a source of vitamins, essential minerals and trace elements. Pharmacol Ther. 1994 Apr-May;62(1-2):193-220. Review.

Walsh CT, Sandstead HH, Prasad AS, Newberne PM, Fraker PJ. Zinc: health effects and research priorities for the 1990s. Environ Health Perspect. 1994 Jun;102 Suppl 2:5-46. Review.

Strand TA, Chandyo RK, Bahl R, Sharma PR, Adhikari RK, Bhandari N, Ulvik RJ, Molbak 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.

Bates CJ, Evans PH, Dardenne M, Prentice A, Lunn PG, Northrop-Clewes CA, Hoare S, Cole TJ, Horan SJ, Longman SC, et al. A trial of zinc supplementation in young rural Gambian children. Br J Nutr. 1993 Jan;69(1):243-55.

Black RE. Therapeutic and preventive effects of zinc on serious childhood infectious diseases in developing countries. Am J Clin Nutr. 1998 Aug;68(2 Suppl):476S-479S. Review.

Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998 Jul;102(1 Pt 1):1-5.

Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ. 2002 Jun 8;324(7350):1358.

Hambidge KM, Krebs NF, Miller L. Evaluation of zinc metabolism with use of stable-isotope techniques: implications for the assessment of zinc status. Am J Clin Nutr. 1998 Aug;68(2 Suppl):410S-413S. Review.

Chai F, Truong-Tran AQ, Ho LH, Zalewski PD. Regulation of caspase activation and apoptosis by cellular zinc fluxes and zinc deprivation: A review. Immunol Cell Biol. 1999 Jun;77(3):272-8. Review.

Truong-Tran AQ, Carter J, Ruffin R, Zalewski PD. New insights into the role of zinc in the respiratory epithelium. Immunol Cell Biol. 2001 Apr;79(2):170-7. Review.

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.

Lira PI, Ashworth A, Morris SS. Effect of zinc supplementation on the morbidity, immune function, and growth of low-birth-weight, full-term infants in northeast Brazil. Am J Clin Nutr. 1998 Aug;68(2 Suppl):418S-424S.

Bhandari N, Bahl R, Taneja S, Strand T, Molbak 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.

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.

Bhandari N, Bahl R, Hambidge KM, Bhan MK. Increased diarrhoeal and respiratory morbidity in association with zinc deficiency--a preliminary report. Acta Paediatr. 1996 Feb;85(2):148-50.

Sazawal S, Black RE, Bhan MK, Jalla S, Sinha A, Bhandari N. Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea--a community-based, double-blind, controlled trial. Am J Clin Nutr. 1997 Aug;66(2):413-8.

Sazawal S, Black RE, Bhan MK, Bhandari N, Sinha A, Jalla S. Zinc supplementation in young children with acute diarrhea in India. N Engl J Med. 1995 Sep 28;333(13):839-44.

Sazawal S, Black RE, Bhan MK, Jalla S, Sinha A, Bhandari N. Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea--a community-based, double-blind, controlled trial. Am J Clin Nutr. 1997 Aug;66(2):413-8.

[No authors listed] Integrated management of the sick child. Bull World Health Organ. 1995;73(6):735-40.

Study ID Numbers:  003740; 003740(Eur. Comm. INCO); NUFU PRO 36/2002
Last Updated:  September 7, 2005
Record first received:  September 6, 2005
ClinicalTrials.gov Identifier:  NCT00148733
Health Authority: Norway: The National Committees for Research Ethics in Norway
ClinicalTrials.gov processed this record on 2005-09-13

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