MalnutritionPhase 2FLACSAM-PKNCT02746276
Optimising Antibiotic Treatment for Sick Malnourished Children
A Phase 2 study testing Ceftriaxone and Metronidazole in people with Malnutrition, run by University of Oxford at 1 site in Kenya.
Trial summary
Children with severe malnutrition who are admitted sick to hospitals have a high mortality, usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics. However, policymakers are not sure that the current antibiotics are the most effective. Read more about this study
- Who is it for?
- Ages 2 to 59 months
- Conditions the study is for
- Malnutrition
- What is being tested?
- Ceftriaxone and Metronidazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteKenya
- Study dates
- 1 Apr 2016to 30 Sep 2017
- Phase
- Phase 2
- 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 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Severe acute malnutrition(SAM) defined as:
- Children aged 6 to 59 months with kwashiorkor; or Mid-Upper Arm Circumference (MUAC) <11.5cm; or weight-for height Z score <-3;
- Children aged 2 to 5 months with kwashiorkor; or MUAC <11cm; or weight-for height Z score <-3; and weight >2.5 kilograms(kg);
- Eligible to receive intravenous antibiotics according to current national guidelines
- For faecal carriage: children aged 2 to 59 months with and without SAM (as defined above) who are admitted to hospital with a syndrome requiring antimicrobial treatment under current national guidelines.
Who cannot join
- Admitted as a transfer from another hospital.
- Known ceftriaxone or metronidazole administration within the previous 7 days (pharmacokinetics(PK) study only).
- Known allergy or contraindication to ceftriaxone or metronidazole (including penicillin allergy) (PK study only).
- A specific clinical indication for another class of antibiotic (PK study only).
- Concurrent participation in a clinical trial (PK study only).
- Attending clinician's judgement that the child is so severely ill that adequate communication about the study with the parent or legal guardian is not possible.
- Refusal of consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics of Antimicrobials and Carriage of Antimicrobial Resistance Amongst Hospitalised Children With Severe Acute Malnutrition
Children with severe malnutrition who are admitted sick to hospitals have a high mortality, usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics. However, policymakers are not sure that the current antibiotics are the most effective. It is possible that the antibiotics that are currently used as second-line should be used first. Finding this out will need a large trial comparing different antibiotics. To prepare for such a trial the investigators first want to make sure that the doses given are correct for malnourished children. The investigators also want to check whether malnourished children more commonly carry resistant bacteria in their feces than well-nourished children. The study is important because the types of antibiotics and the doses needed to fight infection may be different in malnourished children because of the changes in their body due to malnutrition and the types of bacteria present.
Read the detailed description
Children with complicated severe acute malnutrition (SAM) admitted to hospital in sub-Saharan Africa have an inpatient case fatality of 10 to 20%. Because children with SAM may not exhibit the usual signs of infection, World Health Organization (WHO) guidelines recommend routine antibiotics. However this is based on "low quality evidence". There is evidence from Centre for Geographic Medical Research - Coast (CGMR-C), Kilifi and from other centres in Africa that bacterial resistance to the currently recommended first-line antibiotics (gentamicin plus ampicillin or penicillin) may be a problem. It is possible that because of frequent illness and antibiotic exposure, malnourished children may be more likely to have resistant bacteria. Some hospitals in Africa are already increasing use of ceftriaxone as a first-line treatment. However, this is not based on any data that ceftriaxone actually improves outcomes. Of concern is that ceftriaxone use may also lead to further problems with antimicrobial resistance, including inducing extended spectrum beta-lactamase (ESBL) and other classes of resistance.
A further area where evidence for policy is lacking is on the use of metronidazole in severely malnourished children. The WHO guidelines recommend "Metronidazole 7.5 mg/kg every 8 h for 7 days may be given in addition to broad-spectrum antibiotics; however, the efficacy of this treatment has not been established in clinical trials." Metronidazole is effective against Giardia, which is common amongst children with SAM; and against other anaerobic infections, including small bowel bacterial overgrowth and Clostridium difficile colitis. Small cohort studies suggest there may be benefits for nutritional recovery. In Jamaica, half of the children admitted for nutritional rehabilitation had evidence of small bowel anaerobic bacterial overgrowth and this was improved by metronidazole. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also cause liver and neurological toxicity. One small study of metronidazole in children with SAM conducted in in Mexico reported significantly prolonged clearance in SAM, without symptomatic toxicity, but suggesting a dosing frequency reduction. Overall, very few pharmacokinetic studies have been done in malnourished children. Changes in body composition as well as metabolic and drug elimination mechanisms may alter the potential toxicity or effective dose.
The investigators are planning a large clinical trial to assess the efficacy of ceftriaxone and metronidazole on mortality, nutritional recovery and antimicrobial resistance in sick, severely malnourished children. This preparatory work aims to determine the pharmacokinetics of ceftriaxone and metronidazole in 80 severely malnourished children who are admitted to three hospitals in Kenya in order to ensure dosing for the main trial is safe and in the therapeutic range. The study will also determine the frequency of faecal carriage of antimicrobial resistant enteric bacteria at presentation to hospital and at discharge following exposure to antibiotics and the hospital environment, comparing 360 children with, and 360 children without severe malnutrition at three different hospitals. Clear data on the benefits, risks and pharmacokinetics of these antimicrobials will influence policy on case management and antimicrobial stewardship in this vulnerable population.
- Conditions
- Malnutrition
- Being tested
- Ceftriaxone, Metronidazole
- Keywords
- malnutrition, antibiotics, antimicrobial resistance, pharmacokinetics
- Medical subject headings
- Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CeftriaxoneDrug
Also called Rocephin
Ceftriaxone is active against a broad spectrum of gram positive and gram negative bacteria, including intracellular bacteria (e.g. Salmonellae, Staphylococci). Its antibacterial effect is dependent on time above the minimum inhibitory concentration(MIC). Ceftriaxone is highly protein-bound and elimination depends on glomerular filtration rate. In severely ill adults, elimination is highly variable. Alteration in plasma proteins, volume of distribution and renal function in sick severely malnourished children could significantly alter pharmacokinetics (PK). Despite several published studies on the PK of ceftriaxone in children, none have included severe malnutrition.
MetronidazoleDrug
Also called Flagyl
Metronidazole is effective against Giardia, which is common amongst children with SAM; and against other anaerobic infections, including small bowel bacterial overgrowth and Clostridium difficile colitis. Small cohort studies suggest there may be benefits for nutritional recovery. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also cause liver and neurological toxicity. Changes in body composition as well as metabolic and drug elimination mechanisms may alter the potential toxicity or effective dose.
| Study group | Role | What they receive |
|---|---|---|
| Ceftriaxone and metronidazole | Other | Pharmacokinetic study of ceftriaxone and metronidazole in malnourished children Receives: Drug: Ceftriaxone; Drug: Metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve (AUC) of ceftriaxone
To determine the pharmacokinetics of intravenous ceftriaxone given at currently recommended dose and frequency amongst severely malnourished, sick children.
Measured: 24 hours
Trough level of metronidazole
To determine the pharmacokinetics of oral metronidazole given at currently recommended dose and frequency amongst severely malnourished, sick children.
Measured: 8, 24, 48 and 72 hours
Secondary outcomes (1)
Prevalence of faecal carriage of extended spectrum beta-lactamase (ESBL)
To determine the frequency of faecal carriage of ESBL at admission to hospital and at discharge amongst children admitted with and without severe malnutrition.
Measured: Through study completion, an average of 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2016 (estimated)
- Study start1 Apr 2016
- Primary completion30 Sep 2016
- Study completion30 Sep 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for MalnutritionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Sparse sample pharmacokinetics study
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi Kenya, University College, London, Centre for Microbiology Research, Kenya Medical Research Institute, Kenya Medical Research Institute
- Responsible party
- Principal investigator, James Berkley, University of Oxford
- Investigators
- James A Berkley, Paediatrics, Principal investigator, KEMRI Wellcome Trust Research Programme and University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02746276
- Sponsor's protocol ID
- OXTREC 47-15
- Other IDs
- KEMRI/SERU/CGMR-C/023/3161
- Acronym
- FLACSAM-PK
- Status last verified
- Jun 2017
- First submitted
- 4 Apr 2016
- Last updated
- 2 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Yes. Data sharing will be considered by the investigators, then by applying to the Data Governance Committee at CGMR,C who will ensure that appropriate ethical approval is in place for any new analysis.
Publications
Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R; Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013 Aug 3;382(9890):427-451. doi: 10.1016/S0140-6736(13)60937-X. Epub 2013 Jun 6.
PubMed 23746772Bejon P, Mohammed S, Mwangi I, Atkinson SH, Osier F, Peshu N, Newton CR, Maitland K, Berkley JA. Fraction of all hospital admissions and deaths attributable to malnutrition among children in rural Kenya. Am J Clin Nutr. 2008 Dec;88(6):1626-31. doi: 10.3945/ajcn.2008.26510.
PubMed 19064524Talbert A, Thuo N, Karisa J, Chesaro C, Ohuma E, Ignas J, Berkley JA, Toromo C, Atkinson S, Maitland K. Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome. PLoS One. 2012;7(6):e38321. doi: 10.1371/journal.pone.0038321. Epub 2012 Jun 4.
PubMed 22675542Heikens GT, Bunn J, Amadi B, Manary M, Chhagan M, Berkley JA, Rollins N, Kelly P, Adamczick C, Maitland K, Tomkins A; Blantyre Working Group. Case management of HIV-infected severely malnourished children: challenges in the area of highest prevalence. Lancet. 2008 Apr 12;371(9620):1305-7. doi: 10.1016/S0140-6736(08)60565-6. No abstract available.
PubMed 18406865Chimhuya S, Kambarami RA, Mujuru H. The levels of malnutrition and risk factors for mortality at Harare Central Hospital-Zimbabwe: an observation study. Cent Afr J Med. 2007 May-Aug;53(5-8):30-4. doi: 10.4314/cajm.v53i5-8.62612.
PubMed 20355679Fergusson P, Tomkins A. HIV prevalence and mortality among children undergoing treatment for severe acute malnutrition in sub-Saharan Africa: a systematic review and meta-analysis. Trans R Soc Trop Med Hyg. 2009 Jun;103(6):541-8. doi: 10.1016/j.trstmh.2008.10.029. Epub 2008 Dec 5.
PubMed 19058824Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ, Maleta KM, Manary MJ. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med. 2013 Jan 31;368(5):425-35. doi: 10.1056/NEJMoa1202851.
PubMed 23363496Berkley JA, Lowe BS, Mwangi I, Williams T, Bauni E, Mwarumba S, Ngetsa C, Slack MP, Njenga S, Hart CA, Maitland K, English M, Marsh K, Scott JA. Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med. 2005 Jan 6;352(1):39-47. doi: 10.1056/NEJMoa040275.
PubMed 15635111Tansarli GS, Poulikakos P, Kapaskelis A, Falagas ME. Proportion of extended-spectrum beta-lactamase (ESBL)-producing isolates among Enterobacteriaceae in Africa: evaluation of the evidence--systematic review. J Antimicrob Chemother. 2014 May;69(5):1177-84. doi: 10.1093/jac/dkt500. Epub 2014 Jan 6.
PubMed 24398340Babirekere-Iriso E, Musoke P, Kekitiinwa A. Bacteraemia in severely malnourished children in an HIV-endemic setting. Ann Trop Paediatr. 2006 Dec;26(4):319-28. doi: 10.1179/146532806X152845.
PubMed 17132297Acquah SE, Quaye L, Sagoe K, Ziem JB, Bromberger PI, Amponsem AA. Susceptibility of bacterial etiological agents to commonly-used antimicrobial agents in children with sepsis at the Tamale Teaching Hospital. BMC Infect Dis. 2013 Feb 18;13:89. doi: 10.1186/1471-2334-13-89.
PubMed 23419199Blomberg B, Manji KP, Urassa WK, Tamim BS, Mwakagile DS, Jureen R, Msangi V, Tellevik MG, Holberg-Petersen M, Harthug S, Maselle SY, Langeland N. Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study. BMC Infect Dis. 2007 May 22;7:43. doi: 10.1186/1471-2334-7-43.
PubMed 17519011Aiken AM, Mturi N, Njuguna P, Mohammed S, Berkley JA, Mwangi I, Mwarumba S, Kitsao BS, Lowe BS, Morpeth SC, Hall AJ, Khandawalla I, Scott JAG; Kilifi Bacteraemia Surveillance Group. Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study. Lancet. 2011 Dec 10;378(9808):2021-2027. doi: 10.1016/S0140-6736(11)61622-X. Epub 2011 Nov 29.
PubMed 22133536Garot D, Respaud R, Lanotte P, Simon N, Mercier E, Ehrmann S, Perrotin D, Dequin PF, Le Guellec C. Population pharmacokinetics of ceftriaxone in critically ill septic patients: a reappraisal. Br J Clin Pharmacol. 2011 Nov;72(5):758-67. doi: 10.1111/j.1365-2125.2011.04005.x.
PubMed 21545483Lazzerini M, Tickell D. Antibiotics in severely malnourished children: systematic review of efficacy, safety and pharmacokinetics. Bull World Health Organ. 2011 Aug 1;89(8):594-607. doi: 10.2471/BLT.10.084715. Epub 2011 May 20.
PubMed 21836758
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Antimicrobials and Carriage of Antimicrobial Resistance Amongst Hospitalised Children With Severe Acute Malnutrition
- ClinicalTrials.gov ID
- NCT02746276
- Acronym / sponsor ID
- FLACSAM-PK / OXTREC 47-15
- Conditions
- Malnutrition
- Keywords
- malnutrition, antibiotics, antimicrobial resistance, pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 81 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi Kenya, University College, London, Centre for Microbiology Research, Kenya Medical Research Institute, Kenya Medical Research Institute
- Study start
- 1 Apr 2016 (actual)
- Primary completion
- 30 Sep 2016 (actual)
- Study completion
- 30 Sep 2017 (estimated)
- First posted
- 21 Apr 2016 (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.
Children with severe malnutrition who are admitted sick to hospitals have a high mortality, usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics. However, policymakers are not sure that the current antibiotics are the most effective. It is possible that the antibiotics that are currently used as second-line should be used first. Finding this out will need a large trial comparing different antibiotics. To prepare for such a trial the investigators first want to make sure that the doses given are correct for malnourished children. The investigators also want to check whether malnourished children more commonly carry resistant bacteria in their feces than well-nourished children. The study is important because the types of antibiotics and the doses needed to fight infection may be different in malnourished children because of the changes in their body due to malnutrition and the types of bacteria present.
Detailed description
Children with complicated severe acute malnutrition (SAM) admitted to hospital in sub-Saharan Africa have an inpatient case fatality of 10 to 20%. Because children with SAM may not exhibit the usual signs of infection, World Health Organization (WHO) guidelines recommend routine antibiotics. However this is based on "low quality evidence". There is evidence from Centre for Geographic Medical Research - Coast (CGMR-C), Kilifi and from other centres in Africa that bacterial resistance to the currently recommended first-line antibiotics (gentamicin plus ampicillin or penicillin) may be a problem. It is possible that because of frequent illness and antibiotic exposure, malnourished children may be more likely to have resistant bacteria. Some hospitals in Africa are already increasing use of ceftriaxone as a first-line treatment. However, this is not based on any data that ceftriaxone actually improves outcomes. Of concern is that ceftriaxone use may also lead to further problems with antimicrobial resistance, including inducing extended spectrum beta-lactamase (ESBL) and other classes of resistance.
A further area where evidence for policy is lacking is on the use of metronidazole in severely malnourished children. The WHO guidelines recommend "Metronidazole 7.5 mg/kg every 8 h for 7 days may be given in addition to broad-spectrum antibiotics; however, the efficacy of this treatment has not been established in clinical trials." Metronidazole is effective against Giardia, which is common amongst children with SAM; and against other anaerobic infections, including small bowel bacterial overgrowth and Clostridium difficile colitis. Small cohort studies suggest there may be benefits for nutritional recovery. In Jamaica, half of the children admitted for nutritional rehabilitation had evidence of small bowel anaerobic bacterial overgrowth and this was improved by metronidazole. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also cause liver and neurological toxicity. One small study of metronidazole in children with SAM conducted in in Mexico reported significantly prolonged clearance in SAM, without symptomatic toxicity, but suggesting a dosing frequency reduction. Overall, very few pharmacokinetic studies have been done in malnourished children. Changes in body composition as well as metabolic and drug elimination mechanisms may alter the potential toxicity or effective dose.
The investigators are planning a large clinical trial to assess the efficacy of ceftriaxone and metronidazole on mortality, nutritional recovery and antimicrobial resistance in sick, severely malnourished children. This preparatory work aims to determine the pharmacokinetics of ceftriaxone and metronidazole in 80 severely malnourished children who are admitted to three hospitals in Kenya in order to ensure dosing for the main trial is safe and in the therapeutic range. The study will also determine the frequency of faecal carriage of antimicrobial resistant enteric bacteria at presentation to hospital and at discharge following exposure to antibiotics and the hospital environment, comparing 360 children with, and 360 children without severe malnutrition at three different hospitals. Clear data on the benefits, risks and pharmacokinetics of these antimicrobials will influence policy on case management and antimicrobial stewardship in this vulnerable population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Sparse sample pharmacokinetics study
| Arm | Type | Receives |
|---|---|---|
| Ceftriaxone and metronidazole | Other | Drug: Ceftriaxone, Drug: MetronidazolePharmacokinetic study of ceftriaxone and metronidazole in malnourished children |
Who may qualify
- Ages
- 2 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Severe acute malnutrition(SAM) defined as:
- Eligible to receive intravenous antibiotics according to current national guidelines
- For faecal carriage: children aged 2 to 59 months with and without SAM (as defined above) who are admitted to hospital with a syndrome requiring antimicrobial treatment under current national guidelines.
Key exclusion criteria (7 listed)
- Admitted as a transfer from another hospital.
- Known ceftriaxone or metronidazole administration within the previous 7 days (pharmacokinetics(PK) study only).
- Known allergy or contraindication to ceftriaxone or metronidazole (including penicillin allergy) (PK study only).
- A specific clinical indication for another class of antibiotic (PK study only).
- Concurrent participation in a clinical trial (PK study only).
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 |
|---|---|---|
| CeftriaxoneAlso: RocephinCeftriaxone is active against a broad spectrum of gram positive and gram negative bacteria, including intracellular bacteria (e.g. Salmonellae, Staphylococci). Its antibacterial effect is dependent on time above the minimum inhibitory concentration(MIC). Ceftriaxone is highly protein-bound and elimination depends on glomerular filtration rate. In severely ill adults, elimination is highly variable. Alteration in plasma proteins, volume of distribution and renal function in sick severely malnourished children could significantly alter pharmacokinetics (PK). Despite several published studies on the PK of ceftriaxone in children, none have included severe malnutrition. | Drug | Ceftriaxone and metronidazole |
| MetronidazoleAlso: FlagylMetronidazole is effective against Giardia, which is common amongst children with SAM; and against other anaerobic infections, including small bowel bacterial overgrowth and Clostridium difficile colitis. Small cohort studies suggest there may be benefits for nutritional recovery. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also cause liver and neurological toxicity. Changes in body composition as well as metabolic and drug elimination mechanisms may alter the potential toxicity or effective dose. | Drug | Ceftriaxone and metronidazole |
Primary outcome
Area under the curve (AUC) of ceftriaxone
Time frame: 24 hours
To determine the pharmacokinetics of intravenous ceftriaxone given at currently recommended dose and frequency amongst severely malnourished, sick children.
Trough level of metronidazole
Time frame: 8, 24, 48 and 72 hours
To determine the pharmacokinetics of oral metronidazole given at currently recommended dose and frequency amongst severely malnourished, sick children.
1 secondary outcome
Prevalence of faecal carriage of extended spectrum beta-lactamase (ESBL)
Time frame: Through study completion, an average of 5 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 23746772Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R; Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013 Aug 3;382(9890):427-451. doi: 10.1016/S0140-6736(13)60937-X. Epub 2013 Jun 6.
- Background: PubMed 19064524Bejon P, Mohammed S, Mwangi I, Atkinson SH, Osier F, Peshu N, Newton CR, Maitland K, Berkley JA. Fraction of all hospital admissions and deaths attributable to malnutrition among children in rural Kenya. Am J Clin Nutr. 2008 Dec;88(6):1626-31. doi: 10.3945/ajcn.2008.26510.
- Background: PubMed 22675542Talbert A, Thuo N, Karisa J, Chesaro C, Ohuma E, Ignas J, Berkley JA, Toromo C, Atkinson S, Maitland K. Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome. PLoS One. 2012;7(6):e38321. doi: 10.1371/journal.pone.0038321. Epub 2012 Jun 4.
- Background: PubMed 18406865Heikens GT, Bunn J, Amadi B, Manary M, Chhagan M, Berkley JA, Rollins N, Kelly P, Adamczick C, Maitland K, Tomkins A; Blantyre Working Group. Case management of HIV-infected severely malnourished children: challenges in the area of highest prevalence. Lancet. 2008 Apr 12;371(9620):1305-7. doi: 10.1016/S0140-6736(08)60565-6. No abstract available.
- Background: PubMed 20355679Chimhuya S, Kambarami RA, Mujuru H. The levels of malnutrition and risk factors for mortality at Harare Central Hospital-Zimbabwe: an observation study. Cent Afr J Med. 2007 May-Aug;53(5-8):30-4. doi: 10.4314/cajm.v53i5-8.62612.
- Background: PubMed 19058824Fergusson P, Tomkins A. HIV prevalence and mortality among children undergoing treatment for severe acute malnutrition in sub-Saharan Africa: a systematic review and meta-analysis. Trans R Soc Trop Med Hyg. 2009 Jun;103(6):541-8. doi: 10.1016/j.trstmh.2008.10.029. Epub 2008 Dec 5.
- Background: PubMed 23363496Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ, Maleta KM, Manary MJ. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med. 2013 Jan 31;368(5):425-35. doi: 10.1056/NEJMoa1202851.
- Background: PubMed 15635111Berkley JA, Lowe BS, Mwangi I, Williams T, Bauni E, Mwarumba S, Ngetsa C, Slack MP, Njenga S, Hart CA, Maitland K, English M, Marsh K, Scott JA. Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med. 2005 Jan 6;352(1):39-47. doi: 10.1056/NEJMoa040275.
- Background: PubMed 24398340Tansarli GS, Poulikakos P, Kapaskelis A, Falagas ME. Proportion of extended-spectrum beta-lactamase (ESBL)-producing isolates among Enterobacteriaceae in Africa: evaluation of the evidence--systematic review. J Antimicrob Chemother. 2014 May;69(5):1177-84. doi: 10.1093/jac/dkt500. Epub 2014 Jan 6.
- Background: PubMed 17132297Babirekere-Iriso E, Musoke P, Kekitiinwa A. Bacteraemia in severely malnourished children in an HIV-endemic setting. Ann Trop Paediatr. 2006 Dec;26(4):319-28. doi: 10.1179/146532806X152845.
- Background: PubMed 23419199Acquah SE, Quaye L, Sagoe K, Ziem JB, Bromberger PI, Amponsem AA. Susceptibility of bacterial etiological agents to commonly-used antimicrobial agents in children with sepsis at the Tamale Teaching Hospital. BMC Infect Dis. 2013 Feb 18;13:89. doi: 10.1186/1471-2334-13-89.
- Background: PubMed 17519011Blomberg B, Manji KP, Urassa WK, Tamim BS, Mwakagile DS, Jureen R, Msangi V, Tellevik MG, Holberg-Petersen M, Harthug S, Maselle SY, Langeland N. Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study. BMC Infect Dis. 2007 May 22;7:43. doi: 10.1186/1471-2334-7-43.
- World Health Organization (2013) Pocket Book of Hospital Care for Children. Geneva.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Yes. Data sharing will be considered by the investigators, then by applying to the Data Governance Committee at CGMR,C who will ensure that appropriate ethical approval is in place for any new analysis.
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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.
James A Berkley, Paediatrics principal investigator
KEMRI Wellcome Trust Research Programme and University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ceftriaxone and Metronidazole in people with Malnutrition, run by University of Oxford at 1 site 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 5 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 2 Jul 2017. 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 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Area under the curve (AUC) of ceftriaxone (time frame: 24 hours). 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 NCT02746276, which also lists 22 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 2 Jul 2017.