Acceptability and Feasibility in the Context of the IMPROVE Trial in Kenya

Liverpool School of Tropical Medicine

Status and phase: Completed; Phase 4

Conditions: Adherence, Treatment; Malaria in Pregnancy

Treatments: Drug: Monthly intermittent preventive treatment with dihydroartemisnin-piperaquine; Drug: Monthly intermittent preventive treatment with sulfadoxine-pyrimethamine; Drug: Monthly intermittent preventive treatment with dihydroartemisnin-piperaquine with targeted information transfer

Study type: Interventional

Funder types: Other

Identifiers

NCT04160026

18-073

Details and patient eligibility

About

This multi-centre study will compare the acceptability, feasibility, cost and incremental cost-effectiveness of intermittent preventive treatment (IPTp) with dihydroartemisinin-piperaquine (DP) with or without azithromycin to the current strategy of IPTp with sulphadoxine-pyrimethamine (SP) to prevent malaria, sexually transmitted and reproductive tract infections in HIV-uninfected pregnant women (IMPROVE).

Full description

Primary objectives:

1. To assess the acceptability, costs and incremental cost-effectiveness of IPTp-DP, with or without AZ, compared to current policy of IPTp-SP in HIV-uninfected pregnant women.
2. To assess the feasibility of delivering IPTp-DP with or without a targeted information transfer intervention among HIV-uninfected pregnant women attending ANC in the routine health system i.e. non-trial settings.

Acceptability, costs and incremental cost-effectiveness will be assessed in the context of the IMPROVE clinical trial in Kenya, Malawi and Tanzania (see NCT02909712).

We will also conduct an 'implementation feasibility' study in the routine setting in adjacent sites to the IMPROVE trial site in Kenya (only), using a 3-arm cluster randomized design to assess systems effectiveness, implementation strength, scalability, and identify potential operational hurdles for scale up. Ministry of health nurses providing routine ANC services will be trained to provide IPTp-DP or given refresher training for current policy (IPTp-SP). The interventions will be implemented for a period of 10 months. Approximately 5-6 months after the start of implementation, delivery effectiveness will be assessed through exit interviews with pregnant women leaving ANC clinics. Women who receive the correct doses of the interventions will be followed up at home 4-5 days after their clinic visit (i.e. no more than 2 days after their 3-day regimen finished) and interviewed about adherence, including pill counts. The quantitative study will be supplemented by a qualitative study to explain the quantitative outcomes and to assess perceptions of scalability of the interventions tested.

Feasibility study Interventions:

Monthly IPTp regimens: Arm 1. Standard single-day stat course of quality-assured SP; Arm 2. Standard 3-day course of 3 to 5 tablets (40/320mg) of DP per day based on bodyweight (Eurartesim®, AlfaSigma, Italy); Arm 3. Same as 2, with additional job aids and IEC materials.

Outcome Measures

Feasibility study:

Primary Outcome - Adherence assessed through home visits: Proportion of pregnant women attending ANC who receive the first dose of IPTp by DOT and the correct number of tablets for subsequent doses (IPTp-DP) visited at home and who have verified they completed the treatment. Where IPTp-SP is given by DOT this is assumed as 100% adherence and that the correct dosage is given.

Secondary outcome - Delivery effectiveness assessed by exit interviews with pregnant women leaving ANC: Proportion of pregnant women attending ANC for their first and second visit in their second or third trimester who receive an appropriate dose with each drug/drug combination. For the IPTp-DP arm, women will be asked whether the first dose was given by DOT and the correct number of tablets for subsequent doses available on exit. For IPTp-SP the full dose should be given by DOT.

Sample sizes:

Feasibility exit interviews (delivery rate): 1,485 pregnant women Feasibility home visits (adherence rate): 744 pregnant women sampled from women enrolled in exit interviews Acceptability among pregnant women: approx. 90 Acceptability among health providers: approx.90

Enrollment: 1,600 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Kenya Government owned health facilities, Level 3 or 4 health facilities
• Pregnant women attending ANC through non-trial health facilities for a scheduled antenatal care visit in the second or third trimester who receive one of the three study interventions depending on which arm is allocated to that health facility

Exclusion criteria

• Mission or private health facilities, Kenya government owned Level 2 or level 5 health facilities, health facilities included in the trial
• Pregnant women accessing private health facilities
• Health facilities, or pregnant women, involved in other malaria or HIV in pregnancy intervention trials or studies.
• Pregnant women in the first trimester, or pregnant women for who their last visit was less than one month ago

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,600 participants in 3 patient groups

IPTp-SP

Active Comparator group

Description:

Arm 1. Standard single-day stat course of quality-assured SP (Fansidar ®) of 3 tablets (500 mg of sulphadoxine and 25 mg of pyrimethamine). SP given monthly

Treatment:

Drug: Monthly intermittent preventive treatment with sulfadoxine-pyrimethamine

IPTp-DP

Experimental group

Description:

Arm 2. Standard 3-day course of 3 to 5 tablets (40/320mg) of DP per day based on bodyweight (Eurartesim®, AlfaSigma, Italy). DP given monthly

Treatment:

Drug: Monthly intermittent preventive treatment with dihydroartemisnin-piperaquine

IPTp-DP Plus

Experimental group

Description:

Arm 3. Standard 3-day course of 3 to 5 tablets (40/320mg) of DP per day based on bodyweight (Eurartesim®, AlfaSigma, Italy) plus targeted information for health providers.

Treatment:

Drug: Monthly intermittent preventive treatment with dihydroartemisnin-piperaquine with targeted information transfer