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

Study Overview
=================
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: 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. 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

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.

Conditions
-----------------
Malaria in Pregnancy, Adherence, Treatment

Intervention / Treatment
-----------------
* 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


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IPTp-SP<br>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 | Drug: Monthly intermittent preventive treatment with sulfadoxine-pyrimethamine<br>* Feasibility study to assess adherence among health providers in antenatal clinics delivering the study interventions in a routine setting and uptake and adherence among pregnant women.<br>* Other names: Control Arm;|
| Experimental: IPTp-DP<br>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 | Drug: Monthly intermittent preventive treatment with dihydroartemisnin-piperaquine<br>* Feasibility study to assess adherence among health providers in antenatal clinics delivering the study interventions in a routine setting and uptake and adherence among pregnant women.<br>* Other names: Dihydroartemisnin- piperaquine -Eurartesim®;|
| Experimental: IPTp-DP Plus<br>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. | Drug: Monthly intermittent preventive treatment with dihydroartemisnin-piperaquine with targeted information transfer<br>* Feasibility study to assess adherence to guidelines among health providers in antenatal clinics delivering the study interventions in a routine setting and uptake and adherence among pregnant women.<br>* Other names: DP Plus;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence in pregnant women | Proportion of pregnant women attending ANC who receive the drug course correctly and who have verified they completed the treatment at home during a home visit. | Assessed 6-10 months after implementation commences | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of service delivery | Proportion of pregnant women attending ANC for their first and second visit in their second or third trimester who receive the drug course correctly on exit from ANC. For IPTp-SP the full dose should be given by DOT. | Assessed 6-10 months after implementation commences |