Clinical trial NCT04160026: Acceptability and Feasibility in the Context of the IMPROVE Trial in Kenya
Official title: Acceptability and Feasibility of IPTp With Dihydroartemisinin-piperaquine With or Without Azithromycin to Prevent Malaria, Sexually Transmitted and Reproductive Tract Infections in HIV-uninfected Pregnant Women (IMPROVE) in Kenya.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria in Pregnancy
Adherence, Treatment
Lead sponsor: Liverpool School of Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Kenya Medical Research Institute
name: Kamuzu University of Health Sciences
name: National Institute for Medical Research, Tanzania
name: London School of Hygiene and Tropical Medicine
name: University of Bergen
name: Kilimanjaro Christian Medical Centre, Tanzania
First posted: 2019-11-12
Enrollment: 1600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The feasibility study is cluster randomised, where a health facility is a cluster.

The acceptability studies are nested within the feasibility study and the IMPROVE clinical trial.
Primary purpose: PREVENTION

Brief summary: 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).

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Adherence in pregnant women
timeFrame: Assessed 6-10 months after implementation commences
Secondary outcomes:
measure: Effectiveness of service delivery
timeFrame: Assessed 6-10 months after implementation commences
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute
Study officials:
affiliation: Liverpool School of Tropical Medicine
name: Jenny Hill, PhD
role: PRINCIPAL_INVESTIGATOR
References: