Condition category
Infections and Infestations
Date applied
18/05/2006
Date assigned
19/06/2006
Last edited
10/04/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Feiko ter Kuile

ORCID ID

Contact details

Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L3 5QA
United Kingdom
+44 (0)151 7053287
terkuile@liverpool.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Intermittent Preventive Therapy Post-Discharge: an innovative approach in the prevention of rebound severe malaria anaemia and mortality in young children - a randomised double-blind placebo controlled multicentre study

Acronym

IPTpd

Study hypothesis

To compare the efficacy of a single treatment course with lumefantrine-artemether (Coartem®) at discharge to three treatment courses with Coartem® given at discharge, 1 and 2 months (intermittent preventive therapy post-discharge [IPTpd]), to standard antimalarial therapy of oral sulfadoxine-pyrimethamine (SP) in Malawi, in the post-discharge management of children, aged 4-59 months, who have recovered from severe malarial anaemia by assessing mean haemoglobin concentration, and the incidence of rebound severe anaemia, clinical malaria and death by 3 and 6 months.

As of 22/04/2010 this record was updated; all changes can be found in the relevant fields with the above update date. At this time, the anticipated end date of this trial was also updated; the initial anticipated end date at the time of registration was 01/12/2008.

Ethics approval

Approved by College of Medicine Research and Ethics Committee on 25/02/05, reference number: P.03/04/287 and by Liverpool Research and Ethics Committee on 09/02/05, reference number: 05.01

Study design

Randomised, double-blind, placebo-controlled, multicentre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Severe malarial anaemia

Intervention

Patients are randomised into one of the following groups:
Group A - lumefantrine-artemether, single 3-day course at enrolment
Group B - lumefantrine-artemether, three 3-day courses (at enrolment, at 1 month, and at 2 months)
Group C - sulfadoxine-pyrimethamine (SP), single dose at enrolment (added 22/04/2010: group C dropped out following amendments to protocol)

Intervention type

Drug

Phase

Not Specified

Drug names

lumefantrine-artemether (Coartem®), sulfadoxine-pyrimethamine

Primary outcome measures

Current information as of 22/04/2010:
The incidence of rebound severe anaemia (Hb less than 5 g/L), severe malaria (hospital admissions requiring quinine) or death (a composite endpoint) between 1 and 6 months after enrolment.

Initial information at time of registration:
Mean haemoglobin at three months

Secondary outcome measures

Current information as of 22/04/2010:
1. The incidence of sick-child's clinic visits due to clinical malaria by 3 and 6 months
2. The incidence of all-cause sick-child's clinic visits by 3 and 6 months
3. The incidence of all cause re-hospitalisation between 1 - 3 and 1 - 6 months after enrolment
4. The incidence of the three individual components of the composite endpoint (severe anaemia, severe malaria, death) between 1 - 3 and 1 - 6 months after enrolment
5. Mean haemoglobin at 6 months
6. Incidence of adverse events by 3 and 6 months
7. Mean corrected heart rate (QTc) prolongation by 3 days

Initial information at time of registration:
1. The incidence of sick-child's clinic visits due to clinical malaria by 3 and 6 months
2. The incidence of rebound severe anaemia (Hb <5 g/l)
3. The incidence of death by 3 and 6 months
4. Mean haemoglobin at 6 months
5. Incidence of adverse events by 3 and 6 months
6. Mean corrected heart rate (QTc) prolongation by 3 days

Overall trial start date

22/05/2006

Overall trial end date

01/12/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Haemoglobin <5.0 g/dl or packed cell volume (PCV) <15% on admission to the hospital
2. Plasmodium falciparum malaria (any documented parasitaemia) at the time of admission to the hospital or within 24 hours prior to admission
3. Aged between 4 months (inclusive) and 59 months (inclusive) at the time of randomization
4. Bodyweight >5 kg at the time of randomization
5. Subject completed blood transfusion(s) in accordance with routine hospital practice
6. Subject completed intravenous (IV) quinine in accordance with routine hospital practice
7. Able to feed (for breastfed children) or eat (for older children)
8. Able to sit unaided
9. Provision of informed consent by parent or guardian

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

1280 (initial). As of 22/04/2010: 1650 participants or 126 events

Participant exclusion criteria

1. Recognised, specific other cause of severe anaemia at the time of admission to the hospital (e.g. trauma, haematological malignancy, known bleeding disorder, known sickle cell disease)
2. Previous enrolment in the present study
3. Severe anaemia (haemoglobin <5.0 g/dl ) at the time of randomization
4. Known hypersensitivity to any of the study drugs
5. Documented intake of Coartem® (≥4 doses) or SP within 1 week prior to admission
6. Child resides outside of catchment area during the course of the study (6 months)
7. Known need at the time of randomization for concomitant prohibited medication during the 2 months randomized treatment period
8. Ongoing participation into another clinical trial involving ongoing or scheduled treatment with medicinal products during the course of the study (6 months)
9. Known need, or scheduled surgery during the course of the study (6 months)
10. Suspected non-compliance with the follow-up schedule

Recruitment start date

22/05/2006

Recruitment end date

01/12/2010

Locations

Countries of recruitment

Malawi

Trial participating centre

Liverpool School of Tropical Medicine
Liverpool
L3 5QA
United Kingdom

Sponsor information

Organisation

Liverpool School of Tropical Medicine (UK)

Sponsor details

Pembroke Place
Liverpool
L3 5QA
United Kingdom
+44 (0)151 7053281
hemingway@liverpool.ac.uk

Sponsor type

University/education

Website

http://www.liverpool.ac.uk/lstm

Funders

Funder type

Research organisation

Funder name

The Netherlands-African partnership for capacity development and clinical interventions against poverty-related diseases (NACCAP) (Netherlands) (ref: W 07.05.202.00)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

UBS Optimus Foundation (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22172305

Publication citations

  1. Results

    Phiri K, Esan M, van Hensbroek MB, Khairallah C, Faragher B, ter Kuile FO, Intermittent preventive therapy for malaria with monthly artemether-lumefantrine for the post-discharge management of severe anaemia in children aged 4-59 months in southern Malawi: a multicentre, randomised, placebo-controlled trial., Lancet Infect Dis, 2012, 12, 3, 191-200, doi: 10.1016/S1473-3099(11)70320-6.

Additional files

Editorial Notes