Malnutrition SeverePhase 3FLACSAMNCT03174236
First Line Antimicrobials in Children With Complicated Severe Acute Malnutrition
A Phase 3 study testing Ceftriaxone, Benzyl penicillin and Metronidazole in people with Malnutrition Severe and Antibiotic Resistance, run by University of Oxford at 8 sites in 2 countries.
Trial summary
Children with severe malnutrition who are admitted sick to hospitals have a high mortality(death rate), usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics(medication used to kill bacteria). Read more about this study
- Who is it for?
- Ages 2 months to 13 years
- Conditions the study is for
- Malnutrition Severe, Antibiotic Resistance, Antibiotic Toxicity
- What is being tested?
- Ceftriaxone, Benzyl penicillin and Metronidazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,000 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 4 Sep 2017to 31 Dec 2020
- 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 13 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 2 months to 13 years inclusive
- Severe malnutrition defined as:
- kwashiorkor at any age or:
- for children between 2 to 5 months: MUAC <11cm or weight-for length Z score <-3
- for children between 6 to 59 months: MUAC <11.5cm or weight-for length Z score <-3
- for children between 5 to 13 years: MUAC <11.5cm or BMI-for-age Z score <-3
Show all 9Show fewer
- Admitted to hospital and eligible for intravenous antibiotics according to WHO guidelines
- Planning to remain within the hospital catchment area and willing to come for specified visits during the 90 day follow up period
- Informed consent provided by the parents/guardian
Who cannot join
- Known allergy or contraindication to penicillin, gentamicin, ceftriaxone or metronidazole
- A specific and documented clinical indication for another class of antibiotic
- Previously enrolled in this study
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Kenya7 sites
Kemri Wellcome Trust Research Programme
Kilifi, Coast Province, 80108
Kilifi County Hospital
Kilifi, Coast, 80108
KEMRI WT Clinical Trials Facility
Kilifi, 80800
Kilifi County Hospital
Kilifi
Coast General Hospital - Study site
Mombasa
Mbagathi District Hospital
Nairobi
Mbagathi Hospital
Nairobi
About this study
Children with severe malnutrition who are admitted sick to hospitals have a high mortality(death rate), usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics(medication used to kill bacteria). However, the current antibiotics used in hospitals may not be the most effective. It is possible that the antibiotics that are currently used after initial antibiotics should be used first. No studies have been carried out to determine if the current antibiotics used for treating malnourished children who are sick and admitted in hospital are the most appropriate. The aim of this study is to find out if a changed antibiotic system for children with malnutrition is safe, reduces the risk of death and improves nutritional recovery.
Read the detailed description
Children with complicated severe acute malnutrition (SAM) admitted to hospital in sub-Saharan Africa have a case fatality(death rate) between 12% and more than 20%. Because children with SAM may not exhibit the usual signs of infection, WHO guidelines recommend routine antibiotics(medication used to kill bacteria). However, this is based on "low quality evidence". There is evidence that because of bacterial resistance to the currently recommended first-line antibiotics (gentamicin plus ampicillin or penicillin) could be less effective than potential alternatives. 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 increased antimicrobial resistance, including inducing extended spectrum beta-lactamase (ESBL) and other classes of resistance.
A further area where evidence for policy is lacking is 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 anaerobic bacteria, small bowel bacterial overgrowth, Clostridium difficile colitis and also Giardia, which is common amongst children with SAM. Small cohort studies of metronidazole usage suggest there may be benefits for nutritional recovery in malnourished children. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also rarely cause liver and neurological toxicity.
This multi-centre clinical trial will assess the efficacy of two interventions, ceftriaxone and metronidazole, on mortality and nutritional recovery in sick, severely malnourished children in a 2x2 factorial design. There will also be an analysis of antimicrobial resistance and an economic analysis. To extend our understanding of metronidazole and ceftriaxone pharmacokinetics, additional pharmacokinetic data for the dosing schedule used in the trial will be collected from 120 participants in a sub-study. The trial will be conducted at Kilifi County Hospital, Coast General Hospital, Mbagathi Hospital in Kenya and Mbale Regional Referral Hospital in Uganda. The trial will assess antimicrobial resistance that is carried by children in their intestines and in invasive bacterial isolates. A further sub-study will examine the relative costs of care for SAM for health facilities and for families, including antimicrobial usage will also be assessed. Clear data on the benefits, risks and costs of these antimicrobials will influence policy on case management and antimicrobial stewardship in this vulnerable population.
- Being tested
- Ceftriaxone, Benzyl penicillin, Metronidazole, Placebo, Gentamicin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CeftriaxoneDrug
Ceftriaxone a third-generation cephalosporin. Ceftriaxone is active against a broad spectrum of Gram positive and Gram negative bacteria.
Benzyl penicillinDrug
The currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin.
MetronidazoleDrug
The WHO guidelines recommend that Metronidazole may be given in addition to broad-spectrum antibiotics, "however, the efficacy of this treatment has not been established in clinical trials."
PlaceboOther
Suspension manufactured to match metronidazole
GentamicinDrug
The currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin.
| Study group | Role | What they receive |
|---|---|---|
| Ceftriaxone | Experimental | Arm 1 IV Ceftriaxone: Participants in this group receive 80mg/kg IV ceftriaxone once a day for a minimum of 48 hours and a usual maximum of seven days. Receives: Drug: Ceftriaxone |
| Benzyl penicillin plus gentamicin | Active comparator | Arm 2 IV Benzyl penicillin plus gentamicin (usual care): Participants in this group receive 50 000 U/kg IV benzyl penicillin every six hours for a minimum of two days and a maximum of seven days. Receives: Drug: Benzyl penicillin; Drug: Gentamicin |
| Metronidazole | Experimental | Arm 1 Metronidazole: Participants receive 10 to 16 mg/kg oral metronidazole twice a day for seven days. Receives: Drug: Metronidazole |
| Placebo | Placebo comparator | Arm 2 Placebo: Participants receive an oral placebo dose to match that for Metronidazole twice a day for seven days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Mortality is measured using source documents from medical records, verbal autopsy, or death or burial certificates in the community.
Measured: 90 days after enrolment.
Secondary outcomes (13)
Mortality during the first 7 days
Mortality during the first 7 days
Measured: 7 days
Mortality during the first 30 days
Mortality during the first 30 days
Measured: 7 days
Index admission inpatient mortality
Mortality during the index hospitalisation, measured using inpatient records.
Measured: Through index hospital admission, an average of 7 days.
Mortality after discharge from index admission.
Mortality occurring after discharge from the index hospital admission is measured using inpatient medical records, verbal autopsy, or death or burial certificates in the community.
Measured: 90 days after enrolment
Grade 4 toxicity
Grade 4 toxicity events are measured according to the Division of AIDS Tables for Grading the Severity of Adverse Events using medical records.
Measured: Up to 7 days following enrolment
Serious adverse events
Serious adverse events are measured using inpatient and outpatient medical records.
Measured: 90 days after enrolment.
Tolerability - relevant side effects during the first 7 day
Vomiting, diarrhoea, NG tube in place and convulsions during the first 7 days
Measured: 7 days
Causes of death.
Causes of death, as determined by an endpoint review committee.
Measured: 90 days after enrolment
Re-admission to hospital.
Re-admission to hospital defined as at least one overnight stay in a hospital or health facility are measured using inpatient records.
Measured: From discharge from hospital to 90 days after enrolment
Duration of hospitalisation.
Total duration of hospitalisation is measured in days using inpatient records at the start and end of each admission to hospital.
Measured: 90 days after enrolment.
Duration of administration of antibiotics.
Duration of administration of intravenous antibiotics measured using inpatient records.
Measured: 90 days after enrolment.
Change in nutritional status
Change in nutritional status is measured using mid-upper arm circumference, weight-for-length, weight-for-age and length-for-age compared to at enrollment.
Measured: 90 days after enrolment.
Faecal carriage of bacteria expressing Extended Spectrum Lactamase (ESBL)
Faecal carriage of bacteria expressing Extended Spectrum Lactamase (ESBL) is measured using microbial culture and sensitivity testing of rectal swabs.
Measured: Through study completion an average of 90 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2017
- Study start4 Sep 2017
- Primary completion31 Jan 2020
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Malnutrition SevereStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- The trial will investigate two separate antimicrobial interventions in a 2x2 factorial design randomised controlled clinical trial. A factorial design allows more than one intervention to be tested and is useful in assessing a potential package of care. Two randomisations will be made. The two interventions will be analysed separately. Ceftriaxone and metronidazole is an effective and commonly used antibiotic combination, hence major interactions that interfere with efficacy are considered unlikely. However, evidence for interaction between the two interventions will be tested.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London, London School of Hygiene and Tropical Medicine, Swansea Trials Unit, Kenya Medical Research Institute, KEMRI-Wellcome Trust Collaborative Research Program
- Responsible party
- Sponsor
- Investigators
- James A Berkely, FRCPCH, Principal investigator, KEMRI/Wellcome Trust Research Programme & University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03174236
- Sponsor's protocol ID
- KEMRI/SERU/CGMR-C/063/3399
- Other IDs
- 1-17, 105431/Z/14/Z
- Acronym
- FLACSAM
- Status last verified
- May 2020
- First submitted
- 15 May 2017
- Last updated
- 19 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data sharing will be considered by applying to the Data Governance Committee at CGMR,C Kilifi who will manage the process and ensure that appropriate ethical approval is in place and consent has been obtained for uses outside those given in this protocol:DGC@kemri-wellcome.org. Explanation of this eventuality will be included in the participant information and consent form. We intend to share anonymised data with the CHAIN network cohort study (KEMRI/SERU/CGMR-C /054/3318, OxTREC 34-16) which consists of institutions doing studies in malnourished children in Africa and South Asia; to upload anonymised bacterial and resistance sequences on recognised international repositories; and share anonymised bacterial sequence data relating to bacterial resistance with groups working an antimicrobial resistance in Africa and elsewhere.
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 23746772Acquah 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 23419199Talbert 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 19058824Moisi JC, Gatakaa H, Berkley JA, Maitland K, Mturi N, Newton CR, Njuguna P, Nokes J, Ojal J, Bauni E, Tsofa B, Peshu N, Marsh K, Williams TN, Scott JA. Excess child mortality after discharge from hospital in Kilifi, Kenya: a retrospective cohort analysis. Bull World Health Organ. 2011 Oct 1;89(10):725-32, 732A. doi: 10.2471/BLT.11.089235. Epub 2011 Jul 13.
PubMed 22084510Berkley 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 15635111Trehan 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 23363496Babirekere-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 17132297Blomberg 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 22133536Woerther PL, Angebault C, Jacquier H, Hugede HC, Janssens AC, Sayadi S, El Mniai A, Armand-Lefevre L, Ruppe E, Barbier F, Raskine L, Page AL, de Rekeneire N, Andremont A. Massive increase, spread, and exchange of extended spectrum beta-lactamase-encoding genes among intestinal Enterobacteriaceae in hospitalized children with severe acute malnutrition in Niger. Clin Infect Dis. 2011 Oct;53(7):677-85. doi: 10.1093/cid/cir522.
PubMed 21890771Paterson DL. "Collateral damage" from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis. 2004 May 15;38 Suppl 4:S341-5. doi: 10.1086/382690.
PubMed 15127367Jones KD, Hunten-Kirsch B, Laving AM, Munyi CW, Ngari M, Mikusa J, Mulongo MM, Odera D, Nassir HS, Timbwa M, Owino M, Fegan G, Murch SH, Sullivan PB, Warner JO, Berkley JA. Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial. BMC Med. 2014 Aug 14;12:133. doi: 10.1186/s12916-014-0133-2.
PubMed 25189855
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First Line Antimicrobials in Children With Complicated Severe Acute Malnutrition
- ClinicalTrials.gov ID
- NCT03174236
- Acronym / sponsor ID
- FLACSAM / KEMRI/SERU/CGMR-C/063/3399
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University College, London, London School of Hygiene and Tropical Medicine, Swansea Trials Unit, Kenya Medical Research Institute, KEMRI-Wellcome Trust Collaborative Research Program
- Study start
- 4 Sep 2017 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 2 Jun 2017 (actual)
- 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(death rate), usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics(medication used to kill bacteria). However, the current antibiotics used in hospitals may not be the most effective. It is possible that the antibiotics that are currently used after initial antibiotics should be used first. No studies have been carried out to determine if the current antibiotics used for treating malnourished children who are sick and admitted in hospital are the most appropriate. The aim of this study is to find out if a changed antibiotic system for children with malnutrition is safe, reduces the risk of death and improves nutritional recovery.
Detailed description
Children with complicated severe acute malnutrition (SAM) admitted to hospital in sub-Saharan Africa have a case fatality(death rate) between 12% and more than 20%. Because children with SAM may not exhibit the usual signs of infection, WHO guidelines recommend routine antibiotics(medication used to kill bacteria). However, this is based on "low quality evidence". There is evidence that because of bacterial resistance to the currently recommended first-line antibiotics (gentamicin plus ampicillin or penicillin) could be less effective than potential alternatives. 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 increased antimicrobial resistance, including inducing extended spectrum beta-lactamase (ESBL) and other classes of resistance.
A further area where evidence for policy is lacking is 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 anaerobic bacteria, small bowel bacterial overgrowth, Clostridium difficile colitis and also Giardia, which is common amongst children with SAM. Small cohort studies of metronidazole usage suggest there may be benefits for nutritional recovery in malnourished children. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also rarely cause liver and neurological toxicity.
This multi-centre clinical trial will assess the efficacy of two interventions, ceftriaxone and metronidazole, on mortality and nutritional recovery in sick, severely malnourished children in a 2x2 factorial design. There will also be an analysis of antimicrobial resistance and an economic analysis. To extend our understanding of metronidazole and ceftriaxone pharmacokinetics, additional pharmacokinetic data for the dosing schedule used in the trial will be collected from 120 participants in a sub-study. The trial will be conducted at Kilifi County Hospital, Coast General Hospital, Mbagathi Hospital in Kenya and Mbale Regional Referral Hospital in Uganda. The trial will assess antimicrobial resistance that is carried by children in their intestines and in invasive bacterial isolates. A further sub-study will examine the relative costs of care for SAM for health facilities and for families, including antimicrobial usage will also be assessed. Clear data on the benefits, risks and costs of these antimicrobials will influence policy on case management and antimicrobial stewardship in this vulnerable population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- The trial will investigate two separate antimicrobial interventions in a 2x2 factorial design randomised controlled clinical trial. A factorial design allows more than one intervention to be tested and is useful in assessing a potential package of care. Two randomisations will be made. The two interventions will be analysed separately. Ceftriaxone and metronidazole is an effective and commonly used antibiotic combination, hence major interactions that interfere with efficacy are considered unlikely. However, evidence for interaction between the two interventions will be tested.
| Arm | Type | Receives |
|---|---|---|
| Ceftriaxone | Experimental | Drug: CeftriaxoneArm 1 IV Ceftriaxone: Participants in this group receive 80mg/kg IV ceftriaxone once a day for a minimum of 48 hours and a usual maximum of seven days. |
| Benzyl penicillin plus gentamicin | Active comparator | Drug: Benzyl penicillin, Drug: GentamicinArm 2 IV Benzyl penicillin plus gentamicin (usual care): Participants in this group receive 50 000 U/kg IV benzyl penicillin every six hours for a minimum of two days and a maximum of seven days. |
| Metronidazole | Experimental | Drug: MetronidazoleArm 1 Metronidazole: Participants receive 10 to 16 mg/kg oral metronidazole twice a day for seven days. |
| Placebo | Placebo comparator | Other: PlaceboArm 2 Placebo: Participants receive an oral placebo dose to match that for Metronidazole twice a day for seven days. |
Who may qualify
- Ages
- 2 months to 13 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Age 2 months to 13 years inclusive
- Severe malnutrition defined as:
- kwashiorkor at any age or:
- for children between 2 to 5 months: MUAC <11cm or weight-for length Z score <-3
- for children between 6 to 59 months: MUAC <11.5cm or weight-for length Z score <-3
Key exclusion criteria (3 listed)
- Known allergy or contraindication to penicillin, gentamicin, ceftriaxone or metronidazole
- A specific and documented clinical indication for another class of antibiotic
- Previously enrolled in this study
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 |
|---|---|---|
| CeftriaxoneCeftriaxone a third-generation cephalosporin. Ceftriaxone is active against a broad spectrum of Gram positive and Gram negative bacteria. | Drug | Ceftriaxone |
| Benzyl penicillinThe currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin. | Drug | Benzyl penicillin plus gentamicin |
| MetronidazoleThe WHO guidelines recommend that Metronidazole may be given in addition to broad-spectrum antibiotics, "however, the efficacy of this treatment has not been established in clinical trials." | Drug | Metronidazole |
| PlaceboSuspension manufactured to match metronidazole | Other | Placebo |
| GentamicinThe currently recommended first-line antibiotics for the treatment of severe acute malnutrition are gentamicin plus ampicillin or penicillin. | Drug | Benzyl penicillin plus gentamicin |
Primary outcome
Mortality
Time frame: 90 days after enrolment.
Mortality is measured using source documents from medical records, verbal autopsy, or death or burial certificates in the community.
13 secondary outcomes
Mortality during the first 7 days
Time frame: 7 days
Mortality during the first 30 days
Time frame: 7 days
Index admission inpatient mortality
Time frame: Through index hospital admission, an average of 7 days.
Mortality after discharge from index admission.
Time frame: 90 days after enrolment
Grade 4 toxicity
Time frame: Up to 7 days following enrolment
Serious adverse events
Time frame: 90 days after enrolment.
Tolerability - relevant side effects during the first 7 day
Time frame: 7 days
Causes of death.
Time frame: 90 days after enrolment
Re-admission to hospital.
Time frame: From discharge from hospital to 90 days after enrolment
Duration of hospitalisation.
Time frame: 90 days after enrolment.
Duration of administration of antibiotics.
Time frame: 90 days after enrolment.
Change in nutritional status
Time frame: 90 days after enrolment.
Faecal carriage of bacteria expressing Extended Spectrum Lactamase (ESBL)
Time frame: Through study completion an average of 90 days.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2020.
- 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 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 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 22084510Moisi JC, Gatakaa H, Berkley JA, Maitland K, Mturi N, Newton CR, Njuguna P, Nokes J, Ojal J, Bauni E, Tsofa B, Peshu N, Marsh K, Williams TN, Scott JA. Excess child mortality after discharge from hospital in Kilifi, Kenya: a retrospective cohort analysis. Bull World Health Organ. 2011 Oct 1;89(10):725-32, 732A. doi: 10.2471/BLT.11.089235. Epub 2011 Jul 13.
- 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 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.
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- Pocket book of hospital care for children Guidelines for the management of common illnesses with limited resources Author: World Health OrganizationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data sharing will be considered by applying to the Data Governance Committee at CGMR,C Kilifi who will manage the process and ensure that appropriate ethical approval is in place and consent has been obtained for uses outside those given in this protocol:DGC@kemri-wellcome.org. Explanation of this eventuality will be included in the participant information and consent form. We intend to share anonymised data with the CHAIN network cohort study (KEMRI/SERU/CGMR-C /054/3318, OxTREC 34-16) which consists of institutions doing studies in malnourished children in Africa and South Asia; to upload anonymised bacterial and resistance sequences on recognised international repositories; and share anonymised bacterial sequence data relating to bacterial resistance with groups working an antimicrobial resistance in Africa and elsewhere.
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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 Berkely, FRCPCH principal investigator
KEMRI/Wellcome Trust Research Programme & University of Oxford
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ceftriaxone, Benzyl penicillin and Metronidazole in people with Malnutrition Severe and Antibiotic Resistance, run by University of Oxford at 8 sites in 2 countries.
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 9 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: status not confirmed, as of the sponsor's last update on 19 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Kenya, Uganda. 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?
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?
Mortality (time frame: 90 days after enrolment.). 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 NCT03174236, which also lists 25 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 19 May 2020.