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Nutrition DisordersPhase 3CTXNCT00934492

Cotrimoxazole Prophylaxis in Severely Malnourished Children

A Phase 3 study testing Cotrimoxazole dispersible tablet in people with Nutrition Disorders and Life-threatening Infection, run by University of Oxford at 4 sites in Kenya.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This trial aims to test the hypothesis that mortality among Kenyan children with severe malnutrition following initial stabilisation is due to ongoing vulnerability to infectious disease, and that long term daily co-trimoxazole prophylaxis will reduce mortality. Read more about this study

Who is it for?
Ages 2 months to 5 years
What is being tested?
Cotrimoxazole dispersible tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,781 participants
Where
4 sitesKenya
Study dates
Nov 2009to Apr 2014
Phase
Phase 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 months to 5 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Age 2 months to 5 years
  • Admitted to hospital
  • Severe malnutrition: age 6 months to 5 years: MUAC <11cm; age 2 to 6 months: MUAC for age <-3 z scores compared to the WHO growth standards; or kwashiorkor at any age (defined in current WHO guidelines) for enrollments up to 24th March 2011.
  • Severe malnutrition:age 6 months to 5 years: MUAC <11.5cm; age 2 to 6 months: MUAC <11.0cm; or kwashiorkor at any age (defined in current WHO guidelines) for enrollments from 24th March 2011, following protocol amendment.
  • HIV rapid test negative, or if under 18 months, PCR negative and no longer breastfeeding for at least 6 weeks
  • Planning to remain within study area and willing to come for all protocol specified visits

Who cannot join

  • Refusal to give informed consent
  • Cotrimoxazole is specifically contra-indicated (e.g. porphyria)
  • Known hypersensitivity reaction to sulpha drugs or trimethoprim

Trial locations and contacts

4 sites in 1 country.

Kenya4 sites

  • KEMRI/Wellcome Trust Research Programme

    Kilifi, Coast, 80108

  • Malindi District Hospital

    Malindi, Coast

  • Coast Provincial General Hospital

    Mombasa, Coast

  • Mbagathi District Hospital

    Nairobi

Other trials in Kenya

About this study

Official title: Randomized, Placebo Controlled Trial of Cotrimoxazole Prophylaxis Amongst HIV-uninfected Children With Severe Malnutrition

This trial aims to test the hypothesis that mortality among Kenyan children with severe malnutrition following initial stabilisation is due to ongoing vulnerability to infectious disease, and that long term daily co-trimoxazole prophylaxis will reduce mortality.

The objective is to conduct a randomized, double blind, placebo-controlled trial of cotrimoxazole prophylaxis for 6 months among HIV-uninfected children with severe malnutrition following stabilization. The primary outcome will be survival at one year. Secondary outcomes are toxicity, growth, the frequency and causes of hospitalisation and microbial resistance to antibiotics.

Cotrimoxazole has striking protective efficacy against mortality among children with HIV, despite not altering the underlying immune deficiency. It is hypothesised that co-trimoxazole prophylaxis will have a similar effect in children immunocompromised because of severe malnutrition. Worldwide, severe malnutrition is commoner than HIV in childhood and co-trimoxazole is cheap and widely available, making it easily translatable to policy.

Read the detailed description

Malnutrition is the most important underlying risk factor for childhood death in developing countries. Severely malnourished children are at greatly increased risk of death from infectious diseases in the community, in hospital and following discharge. Malnutrition and infection are synergistic, in part because malnutrition causes secondary immune deficiency, whilst infections cause losses and diversion of nutrients. This synergy is exacerbated by a high level of exposure to pathogens. Among children treated for severe malnutrition in Africa, mortality following discharge from hospitals ranges between 8% and 41%.

Cotrimoxazole is a synthetic antibacterial combination that blocks two steps of folate metabolism involved in the biosynthesis of nucleic acids and proteins essential to many bacteria and some parasites, including Plasmodium falciparum. It is cheap, widely available and has an established safety profile in African populations. Cotrimoxazole prophylaxis dramatically reduces mortality among children with HIV, irrespective of the degree of immune suppression. The primary effect is in reducing bacterial infection, especially pneumonia. the effect has been demonstrated in areas with high levels of cotrimoxazole resistance bacteria. It is also widely used in developed countries among children with other immune deficiencies to prevent infection. Children with severe malnutrition are immune deficient, as evidenced by their susceptibility to infectious diseases, and may therefore benefit from daily antimicrobial prophylaxis.

The objective is to conduct a randomized, double blind, placebo-controlled trial of cotrimoxazole prophylaxis for 6 months among HIV-uninfected children with severe malnutrition following stabilization. The primary outcome will be survival at one year. Secondary outcomes are toxicity, growth, hospitalisation, microbial resistance in carriage and pathogenic organisms and markers of inflammation and immune function.

On 26th September 2012, on advice from an independent senior statistician who reviewed the actual event rate in the control arm, the rates of recruitment and loss to follow up, the Trial Steering Committee recommended that the trial team to recruit at least 1750 participants to achieve the original objective of having >90% power to detect a reduction in mortality during 12 months follow up of 33%. Recruitment was stopped on 31st March 2013 at 1781 participants.

Being tested
Cotrimoxazole dispersible tablet, Placebo dispersible tablet
Keywords
Malnutrition, Wasting, Kwashiorkor, Immune deficiency, Infection, Prophylaxis, Mortality, Kenya
Medical subject headings
Nutrition Disorders, Malnutrition, Cachexia, Kwashiorkor, Immunologic Deficiency Syndromes, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cotrimoxazole dispersible tabletDrug

    Also called Cosatrim, Septrin, Bactrim

    Cotrimoxazole dispersible tablets 120/240mg daily for six consecutive months.

  • Placebo dispersible tabletDrug

    Also called Placebo

    Placebo dispersible tablets 120/240mg daily for six consecutive months.

Study groups in NCT00934492
Study groupRoleWhat they receive
Cotrimoxazole dispersible tabletActive comparatorChildren between 2-6 months will receive single dispersible tablet of 120mg,daily while children over 6 months to 5 years will receive 240 mg dispersible tablet daily for six months.
Receives: Drug: Cotrimoxazole dispersible tablet
Placebo dispersible tabletPlacebo comparatorChildren between 2-6 months will receive single dispersible Placebo tablet of 120mg,daily while children over 6 months to 5 years will receive 240 mg dispersible Placebo tablet daily for six months.
Receives: Drug: Placebo dispersible tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mortality

    Measured: 12 months

Secondary outcomes (4)

  1. Frequency and causes of hospital re-admission

    Measured: 12 months

  2. Growth

    Measured: 12 months

  3. Microbial population and antimicrobial resistance

    Measured: 12 months

  4. Immune activation and inflammatory markers; markers of immune function

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionApr 2014
  4. Study completionApr 2014

Resources

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
1,781 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00934492
Sponsor's protocol ID
SSC 1562
Other IDs
OXTREC 18 09, WT 083579
Acronym
CTX
Status last verified
Aug 2014
First submitted
7 Jul 2009
Last updated
18 Aug 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Ngari MM, Iversen PO, Thitiri J, Mwalekwa L, Timbwa M, Fegan GW, Berkley JA. Linear growth following complicated severe malnutrition: 1-year follow-up cohort of Kenyan children. Arch Dis Child. 2019 Mar;104(3):229-235. doi: 10.1136/archdischild-2018-315641. Epub 2018 Sep 28.

    PubMed 30266874

  • Ngari MM, Mwalekwa L, Timbwa M, Hamid F, Ali R, Iversen PO, Fegan GW, Berkley JA. Changes in susceptibility to life-threatening infections after treatment for complicated severe malnutrition in Kenya. Am J Clin Nutr. 2018 Apr 1;107(4):626-634. doi: 10.1093/ajcn/nqy007.

    PubMed 29635501

  • Ngari MM, Thitiri J, Mwalekwa L, Timbwa M, Iversen PO, Fegan GW, Berkley JA. The impact of rickets on growth and morbidity during recovery among children with complicated severe acute malnutrition in Kenya: A cohort study. Matern Child Nutr. 2018 Apr;14(2):e12569. doi: 10.1111/mcn.12569. Epub 2017 Nov 27.

    PubMed 29178404

  • Berkley JA, Ngari M, Thitiri J, Mwalekwa L, Timbwa M, Hamid F, Ali R, Shangala J, Mturi N, Jones KD, Alphan H, Mutai B, Bandika V, Hemed T, Awuondo K, Morpeth S, Kariuki S, Fegan G. Daily co-trimoxazole prophylaxis to prevent mortality in children with complicated severe acute malnutrition: a multicentre, double-blind, randomised placebo-controlled trial. Lancet Glob Health. 2016 Jul;4(7):e464-73. doi: 10.1016/S2214-109X(16)30096-1. Epub 2016 Jun 2.

    PubMed 27265353

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cotrimoxazole dispersible tablet in people with Nutrition Disorders and Life-threatening Infection, run by University of Oxford at 4 sites in Kenya.

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 6 inclusion and 3 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 18 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Kenya. 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 phase mean?

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?

Mortality (time frame: 12 months). 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 NCT00934492, which also lists 4 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 18 Aug 2014.

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