PneumoniaPhase 2/3NCT00252304
Therapeutic Zinc in Childhood Pneumonia
A Phase 2/3 study testing Zinc (zinc sulphate) in people with Pneumonia, run by Centre For International Health at 1 site in Nepal.
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. Read more about this study
- Who is it for?
- Ages 2 to 35 months
- Conditions the study is for
- Pneumonia
- What is being tested?
- Zinc (zinc sulphate)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 641 participants
- Where
- 1 siteNepal
- Study dates
- Jan 2006to Jul 2008
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 35 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Zinc as Adjuvant Therapy in the Treatment of Severe Pneumonia in Nepalese Children at the Kanti Children's Hospital
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.
Read the detailed 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.
- Conditions
- Pneumonia
- Being tested
- Zinc (zinc sulphate), Placebo
- Keywords
- Child, severe pneumonia, Zinc, Nepal, therapeutic
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc (zinc sulphate)Drug
Also called Produced by Nutriset, Malaunay, France
Dissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months
PlaceboDrug
Also called Produced by Nutriset, Malaunay, France
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Zinc | Experimental | Zinc sulphate 10 or 20 mg per day Receives: Drug: Zinc (zinc sulphate) |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to cessation of severe pneumonia
Measured: Within 2 weeks after enrollment
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.
Measured: Recovery from pneumonia within 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2005 (estimated)
- Study startJan 2006
- Primary completionJul 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 641 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre For International Health
- Sponsor type
- University, hospital or other
- Collaborators
- Tribhuvan University, Nepal, Statens Serum Institut, All India Institute of Medical Sciences, Institut de Recherche pour le Developpement, Society for Applied Studies
- Investigators
- Sudha Basnet, MD, Principal investigator, Department of Child Health, Institute of Medicine, Tribhuwan University, Katmandu, NepalTor A Strand, MD, PhD, Study director, Centre For International HealthHalvor Sommerfelt, MD, PhD, Study chair, Centre For International HealthNita Bhandari, MBBS, PhD, Study chair, Centre For International HealthPrakash S Shrestha, MD, Study director, Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj:Ramesh K Adhikari, MD, Study chair, Child Health Research Project, Department of Child Health, Institute of Medicine, Maharajganj:
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00252304
- Sponsor's protocol ID
- INCO-CT-2004-003740-2
- Status last verified
- Oct 2009
- First submitted
- 10 Nov 2005
- Last updated
- 6 Oct 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
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. doi: 10.1093/ajcn/68.2.447S.
PubMed 9701160Bahl 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. doi: 10.1093/ajcn/68.2.414S.
PubMed 9701154Bhutta 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. doi: 10.1016/s0022-3476(99)70086-7.
PubMed 10586170Bhandari 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.
PubMed 12042580Brown 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. doi: 10.1093/ajcn/68.2.425S.
PubMed 9701156Beisel 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
Cousins RJ, Leinart AS. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J. 1988 Oct;2(13):2884-90. doi: 10.1096/fasebj.2.13.2458983.
PubMed 2458983Strand 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. doi: 10.1128/IAI.71.4.2009-2013.2003.
PubMed 12654820Bhutta 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. doi: 10.1093/ajcn/72.6.1516.
PubMed 11101480Strand 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.
PubMed 11986453Brooks 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.
PubMed 15158629Haugen J, Basnet S, Hardang IM, Sharma A, Mathisen M, Shrestha P, Valentiner-Branth P, Strand TA. Vitamin D status is associated with treatment failure and duration of illness in Nepalese children with severe pneumonia. Pediatr Res. 2017 Dec;82(6):986-993. doi: 10.1038/pr.2017.71. Epub 2017 Aug 16.
PubMed 28678771Basnet S, Shrestha PS, Sharma A, Mathisen M, Prasai R, Bhandari N, Adhikari RK, Sommerfelt H, Valentiner-Branth P, Strand TA; Zinc Severe Pneumonia Study Group. A randomized controlled trial of zinc as adjuvant therapy for severe pneumonia in young children. Pediatrics. 2012 Apr;129(4):701-8. doi: 10.1542/peds.2010-3091. Epub 2012 Mar 5.
PubMed 22392179
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Zinc as Adjuvant Therapy in the Treatment of Severe Pneumonia in Nepalese Children at the Kanti Children's Hospital
- ClinicalTrials.gov ID
- NCT00252304
- Acronym / sponsor ID
- INCO-CT-2004-003740-2
- Conditions
- Pneumonia
- Keywords
- Child, severe pneumonia, Zinc, Nepal, therapeutic
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 641 participants (actual)
- Lead sponsor
- Centre For International HealthUniversity, hospital or other
- Collaborators
- Tribhuvan University, Nepal, Statens Serum Institut, All India Institute of Medical Sciences, Institut de Recherche pour le Developpement, Society for Applied Studies
- Study start
- Jan 2006
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 11 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zinc | Experimental | Drug: Zinc (zinc sulphate)Zinc sulphate 10 or 20 mg per day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 2 to 35 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zinc (zinc sulphate)Also: Produced by Nutriset, Malaunay, FranceDissolvable zinc tablet 10 mg elemental zinc per day for infants 20 mg elemental zinc per day for children 12 to 35 months | Drug | Zinc |
| PlaceboAlso: Produced by Nutriset, Malaunay, FrancePlacebo | Drug | Placebo |
Primary outcome
Time to cessation of severe pneumonia
Time frame: Within 2 weeks after enrollment
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.
Time frame: Recovery from pneumonia within 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2009.
- BackgroundNepal Demographic and Health Survey, 2001
- BackgroundNepal Ministry of Health, Department of Health Services Annual Report 2000- 2001, Kathmandu
- Background: PubMed 9701160Shankar 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.
- Background: PubMed 9701154Bahl 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. doi: 10.1093/ajcn/68.2.414S.
- Background: PubMed 10586170Bhutta 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. doi: 10.1016/s0022-3476(99)70086-7.
- Background: PubMed 12042580Bhandari 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.
- Background: PubMed 9701156Brown 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. doi: 10.1093/ajcn/68.2.425S.
- BackgroundBeisel 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
- Background: PubMed 2458983Cousins RJ, Leinart AS. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J. 1988 Oct;2(13):2884-90. doi: 10.1096/fasebj.2.13.2458983.
- Background: PubMed 12654820Strand 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. doi: 10.1128/IAI.71.4.2009-2013.2003.
- Background: PubMed 11101480Bhutta 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. doi: 10.1093/ajcn/72.6.1516.
- Background: PubMed 11986453Strand 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sudha Basnet, MD principal investigator
Department of Child Health, Institute of Medicine, Tribhuwan University, Katmandu, Nepal
Tor A Strand, MD, PhD study director
Centre For International Health
Halvor Sommerfelt, MD, PhD study chair
Centre For International Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Zinc (zinc sulphate) in people with Pneumonia, run by Centre For International Health at 1 site in Nepal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to cessation of severe pneumonia (time frame: Within 2 weeks after enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00252304, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2009.