Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06624631
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-01
Brief Title:
PDMC Implementation Trial in Kenya
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Delivery Strategies for Malaria Chemoprevention in the Post-discharge Management of Children Hospitalised with Severe Anaemia or Severe Malaria Cluster and Individually Randomised Controlled Implementation Trial and Economic Evaluation in Kenya
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PDMC-SL
Brief Summary:
The goal of this implementation trial is to evaluate at least two alternative delivery strategies and adherence support for malaria chemoprevention with dihydroartemisinin-piperaquine in the post-discharge management of children hospitalised with severe anaemia or severe malaria to optimise adherence in Kenya
The actual interventions to be evaluated will be co-designed with national stakeholders during an initial formative research stage
The actual interventions to be evaluated will be co-designed with national stakeholders during an initial formative research stage
Detailed Description:
Study design
A multi-centre 2-arm cluster-randomised trial evaluating two health system delivery strategies and a 3-arm nested individually randomised trial evaluating two new intervention strategies to enhance end-user adherence to post discharge malaria chemoprevention PDMC with dihydroartemisinin-piperaquine compared to the standard of care without adherence strategies
Study sites Health facilities with blood transfusion services in malaria-endemic areas in western Kenya
Study Population
Cluster inclusion criteria health facilities with blood transfusion services offering in-patient care for children with severe anaemia and severe malaria Exclusion criteria primary health facilities without subservient lower-level health facilities
Individual inclusion criteria convalescent children aged 10 years weighing 5 kg admitted with severe anaemia haemoglobin5gdL or severe malaria clinically stable able to take or switch to oral medication post-transfusion Hb 5gdL Exclusion criteria blood loss due to trauma malignancy known bleeding disorders or sickle cell disease known hypersensitivity to study drug known heart conditions non-resident in the study area previous participation in the study known need at enrolment for prohibited medication and scheduled surgery during the 4-month course of the study HIV infection and cotrimoxazole prophylaxis are not exclusion criteria
Study Interventions
Cluster randomised trial Hospitals will be randomised to one of two delivery platforms for PDMC A or B The final choice of the two delivery strategies to be evaluated will be informed by formative research conducted under a separate standalone protocol LSTM Protocol 23-053 KEMR-SERU 4804870 For example these could include A Delivery of PDMC at the primary admitting facility or B Referral to the closest peripheral facility for dispensing of PDMC two weeks after discharge
Individually randomised trial The final choice of the adherence support strategies to be evaluated will be informed by formative research conducted under a separate standalone protocol For example these could include a CHW reminder visits at home b SMSphone call reminders and c no reminders control
All participating children will receive standard in-hospital care for severe anaemia or severe malaria blood transfusion often combined parenteral artesunate followed by a 3-day course of AL whether they initially had malaria or not which will be started in-hospital as soon as they are able to take oral medication Many children are likely to receive parenteral antibiotics as well as part of the standard of care
Primary endpoints
Cluster randomised trial The proportion of eligible participants who were not prescribed the full 3 courses of PDMC
Individually randomised trial The proportion of children with incomplete adherence to the 9 doses of PDMC three courses of 3-day treatments 3x39
Secondary endpoints
1 Clinical effectiveness all-cause and malaria-specific sick-child clinic visits all-cause and cause-specific readmissions and all-cause mortality by the end of week 14 after discharge
2 Safety incidence of serious adverse events
3 Cost-effectiveness
4 Acceptability and feasibility
Follow-up procedures
Children will be followed for 14 weeks ie four weeks after the last PDMC course through passive surveillance of clinic visits and hospitalisations Each child will then be seen for an end-of-study visit towards the end of week 14 Children will also be visited at home for unannounced home visits one to three days from the last day of the last dose of each 3-day course of PDMC medication to assess adherence
Sample size
Cluster randomised trial Approximately 89 participants per cluster cluster size will vary between clusters or approximately 712 overall 356 in each of the two study arms is estimated to provide over 80 power to detect a risk difference of 23 from 35 in the control arm to 12 in the intervention clusters RR045 using a two-sided alpha of 005 and assuming an intra-cluster correlation coefficient ICC of 003 a coefficient of variation of 057 15 loss to follow-up and small-sample correction to account for the small number of clusters
Individually randomised trial A sample size of 147 participants in the control arm c and 147 in each of the two intervention arms a and b totalling 441 participants would provide 90 power to detect a 50 reduction in the primary endpoint proportion of children with incomplete adherence to the 9 doses of PDMC from 368 in the control arm to 184 RR050 in any of the two intervention arms using a 111 allocation after accounting for the multiple comparisons α 0025 A total of 519 participants 173 per arm will be recruited to allow for a 15 loss to follow-up
Data Analysis
Risk ratios and corresponding 95 confidence intervals will be computed to compare treatment effects using multi-level mixed models accounting for clustering effects
A multi-centre 2-arm cluster-randomised trial evaluating two health system delivery strategies and a 3-arm nested individually randomised trial evaluating two new intervention strategies to enhance end-user adherence to post discharge malaria chemoprevention PDMC with dihydroartemisinin-piperaquine compared to the standard of care without adherence strategies
Study sites Health facilities with blood transfusion services in malaria-endemic areas in western Kenya
Study Population
Cluster inclusion criteria health facilities with blood transfusion services offering in-patient care for children with severe anaemia and severe malaria Exclusion criteria primary health facilities without subservient lower-level health facilities
Individual inclusion criteria convalescent children aged 10 years weighing 5 kg admitted with severe anaemia haemoglobin5gdL or severe malaria clinically stable able to take or switch to oral medication post-transfusion Hb 5gdL Exclusion criteria blood loss due to trauma malignancy known bleeding disorders or sickle cell disease known hypersensitivity to study drug known heart conditions non-resident in the study area previous participation in the study known need at enrolment for prohibited medication and scheduled surgery during the 4-month course of the study HIV infection and cotrimoxazole prophylaxis are not exclusion criteria
Study Interventions
Cluster randomised trial Hospitals will be randomised to one of two delivery platforms for PDMC A or B The final choice of the two delivery strategies to be evaluated will be informed by formative research conducted under a separate standalone protocol LSTM Protocol 23-053 KEMR-SERU 4804870 For example these could include A Delivery of PDMC at the primary admitting facility or B Referral to the closest peripheral facility for dispensing of PDMC two weeks after discharge
Individually randomised trial The final choice of the adherence support strategies to be evaluated will be informed by formative research conducted under a separate standalone protocol For example these could include a CHW reminder visits at home b SMSphone call reminders and c no reminders control
All participating children will receive standard in-hospital care for severe anaemia or severe malaria blood transfusion often combined parenteral artesunate followed by a 3-day course of AL whether they initially had malaria or not which will be started in-hospital as soon as they are able to take oral medication Many children are likely to receive parenteral antibiotics as well as part of the standard of care
Primary endpoints
Cluster randomised trial The proportion of eligible participants who were not prescribed the full 3 courses of PDMC
Individually randomised trial The proportion of children with incomplete adherence to the 9 doses of PDMC three courses of 3-day treatments 3x39
Secondary endpoints
1 Clinical effectiveness all-cause and malaria-specific sick-child clinic visits all-cause and cause-specific readmissions and all-cause mortality by the end of week 14 after discharge
2 Safety incidence of serious adverse events
3 Cost-effectiveness
4 Acceptability and feasibility
Follow-up procedures
Children will be followed for 14 weeks ie four weeks after the last PDMC course through passive surveillance of clinic visits and hospitalisations Each child will then be seen for an end-of-study visit towards the end of week 14 Children will also be visited at home for unannounced home visits one to three days from the last day of the last dose of each 3-day course of PDMC medication to assess adherence
Sample size
Cluster randomised trial Approximately 89 participants per cluster cluster size will vary between clusters or approximately 712 overall 356 in each of the two study arms is estimated to provide over 80 power to detect a risk difference of 23 from 35 in the control arm to 12 in the intervention clusters RR045 using a two-sided alpha of 005 and assuming an intra-cluster correlation coefficient ICC of 003 a coefficient of variation of 057 15 loss to follow-up and small-sample correction to account for the small number of clusters
Individually randomised trial A sample size of 147 participants in the control arm c and 147 in each of the two intervention arms a and b totalling 441 participants would provide 90 power to detect a 50 reduction in the primary endpoint proportion of children with incomplete adherence to the 9 doses of PDMC from 368 in the control arm to 184 RR050 in any of the two intervention arms using a 111 allocation after accounting for the multiple comparisons α 0025 A total of 519 participants 173 per arm will be recruited to allow for a 15 loss to follow-up
Data Analysis
Risk ratios and corresponding 95 confidence intervals will be computed to compare treatment effects using multi-level mixed models accounting for clustering effects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None