CHIZAP: Community- and Health Facility-Based Intervention With Zinc as Adjuvant Therapy for Childhood Pneumonia

NCT00148733 | Completed Phase 2 Results DMC

• 3 other identifiers: 003740003740(Eur. Comm. INCO)NUFU PRO 36/2002
• Study Type: interventional
• Target: 2,628
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pneumonia

Keywords

Child; pneumonia; Zinc; clinical trial; Nepal; nutrition; therapeutic

Outcome Measures

Primary Outcomes (5)

• Risk of Treatment Failure.

  Enrolled children will be followed and given zinc or placebo for 14 days. We will compare the proportion with treatment failure (i.e. lack of improvement within 3 days) between the two groups

  Within 2 weeks after enrollment

• Non-injury Clinic Visits and Hospital Admissions After Treatment Has Been Initiated

  We will measure to what extent the intervention can reduce the number of severe events.

  Within 2 weeks after enrollment

• Active and Passive Morbidity Surveillance for Six Months After the 14-day Supplementation Period is Completed

  We will measure to what extent short term zinc administration has an impact on growth and morbidity for up to 6 months after end of supplementation

  six months

• Difference in Growth and Thymic Size Between the Treatment Groups Measured at Three and Six Months After the Zinc Supplementation

  Thymus size will be measured using ultrasonography and compared between the two groups. at two occasions 2.5 and 6 months after end of supplementation

  six months

• Adverse Effects

  Vomiting, regurgitation, pain in abdomen for 15 minutes after zinc or placebo administration.

  14 days

Secondary Outcomes (5)

• Effect Modifiers for the Effect of Zinc Given During Pneumonia

  Within 2 weeks after enrollment

• The Efficacy of Zinc According to Breast Feeding Status and in Different Age Categories

  Within 2 weeks after enrollment

• The Efficacy of Zinc in Malnourished and Non-malnourished Children

  Within 2 weeks after enrollment

• Will Presence of a RNA Virus Modify the Effect of Zinc

  14 days

• Folate, Cobalamin and Vitamin D Status of the Enrolled Children

  14 days

Study Arms (2)

Zinc

EXPERIMENTAL

Zinc sulphate 10 or 20 mg (elemental zinc) per day. Intervention and placebo given perorally mixed with approximately 5 mL of breastmilk or clean water

Drug: Zinc

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Zinc

Interventions

Zinc DRUG

Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months

Also known as: Produced by Nutriset, Malaunay, France

Placebo; Zinc

Eligibility Criteria

• Age: 2 Months - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• The child requires special care for severe illness other than pneumonia
• Severe malnutrition defined as being \< 70% National Center for Health Statistics (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

Sponsors & Collaborators

• Centre For International Health: lead
• Tribhuvan University, Nepal: collaborator
• Statens Serum Institut: collaborator
• All India Institute of Medical Sciences: collaborator
• IRD, Epidemiologie et Prevention, Montpelier, France: collaborator
• Society for Applied Studies: collaborator

Study Sites (1)

Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan

Bhaktapur, P.O.Box 40, Nepal

Location

Related Publications (21)

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• 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. doi: 10.1016/0163-7258(94)90011-6.

  PMID: 7991643 BACKGROUND

• 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(Suppl 2):5-46. doi: 10.1289/ehp.941025.

  PMID: 7925188 BACKGROUND

• 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. doi: 10.1542/peds.109.5.898.

  PMID: 11986453 BACKGROUND

• 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. doi: 10.1079/bjn19930026.

  PMID: 8457531 BACKGROUND

• 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. doi: 10.1093/ajcn/68.2.476S.

  PMID: 9701163 BACKGROUND

• 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. doi: 10.1542/peds.102.1.1.

  PMID: 9651405 BACKGROUND

• 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. doi: 10.1136/bmj.324.7350.1358.

  PMID: 12052800 BACKGROUND

• 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. doi: 10.1093/ajcn/68.2.410S.

  PMID: 9701153 BACKGROUND

• 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. doi: 10.1046/j.1440-1711.1999.00825.x.

  PMID: 10361260 BACKGROUND

• 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. doi: 10.1046/j.1440-1711.2001.00986.x.

  PMID: 11264713 BACKGROUND

• 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. doi: 10.1093/ajcn/68.2.447S.

  PMID: 9701160 BACKGROUND

• 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. doi: 10.1093/ajcn/68.2.418S.

  PMID: 9701155 BACKGROUND

• 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. doi: 10.1542/peds.109.6.e86.

  PMID: 12042580 BACKGROUND

• 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. doi: 10.1016/S0140-6736(04)16252-1.

  PMID: 15158629 BACKGROUND

• 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. doi: 10.1111/j.1651-2227.1996.tb13981.x.

  PMID: 8640039 BACKGROUND

• 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. doi: 10.1093/ajcn/66.2.413.

  PMID: 9250122 BACKGROUND

• 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. doi: 10.1056/NEJM199509283331304.

  PMID: 7651474 BACKGROUND

• Integrated management of the sick child. Bull World Health Organ. 1995;73(6):735-40.

  PMID: 8907767 BACKGROUND

• Haugen J, Chandyo RK, Brokstad KA, Mathisen M, Ulak M, Basnet S, Valentiner-Branth P, Strand TA. Cytokine Concentrations in Plasma from Children with Severe and Non-Severe Community Acquired Pneumonia. PLoS One. 2015 Sep 25;10(9):e0138978. doi: 10.1371/journal.pone.0138978. eCollection 2015.

  PMID: 26407163 DERIVED

• Valentiner-Branth P, Shrestha PS, Chandyo RK, Mathisen M, Basnet S, Bhandari N, Adhikari RK, Sommerfelt H, Strand TA. A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal. Am J Clin Nutr. 2010 Jun;91(6):1667-74. doi: 10.3945/ajcn.2009.28907. Epub 2010 Apr 7.

  PMID: 20375190 DERIVED

MeSH Terms

Conditions

Pneumonia

Interventions

Zinc

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Results Point of Contact

• Title: Tor A Strand
• Organization: University of Bergen

tor.strand@cih.uib.no

90971086

Study Officials

• Tor A Strand, MD PhD

  Centre for International Health, University of Bergen, 5021 Bergen, Norway

  PRINCIPAL INVESTIGATOR

• Halvor Sommerfelt, MD PhD

  Centre for International Health, University of Bergen, 5021 Bergen, Norway

  STUDY DIRECTOR

• Prakash S Shrestha, MD Professor

  Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj

  STUDY DIRECTOR

• Ramesh K Adhikari, MD Dean

  Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj

  STUDY CHAIR

• Palle Valentiner-Branth, MD PhD

  Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: January 1, 2004
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: March 16, 2022
• Results First Posted: February 16, 2015

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

NE (1)