Evaluation of community-level interventions to increase early initiation of antenatal care in pregnancy: protocol for the Community REACH study, a cluster randomised controlled trial with integrated process and economic evaluations.

BACKGROUND: The provision of high-quality maternity services is a priority for reducing inequalities in health outcomes for mothers and infants. Best practice includes women having their initial antenatal appointment within the first trimester of pregnancy in order to provide screening and support for healthy lifestyles, well-being and self-care in pregnancy. Previous research has identified inequalities in access to antenatal care, yet there is little evidence on interventions to improve early initiation of antenatal care. The Community REACH trial will assess the effectiveness and cost-effectiveness of engaging communities in the co-production and delivery of an intervention that addresses this issue. METHODS/DESIGN: The study design is a matched cluster randomised controlled trial with integrated process and economic evaluations. The unit of randomisation is electoral ward. The intervention will be delivered in 10 wards; 10 comparator wards will have normal practice. The primary outcome is the proportion of pregnant women attending their antenatal booking appointment by the 12th completed week of pregnancy. This and a number of secondary outcomes will be assessed for cohorts of women (n = approximately 1450 per arm) who give birth 2-7 and 8-13 months after intervention delivery completion in the included wards, using routinely collected maternity data. Eight hospitals commissioned to provide maternity services in six NHS trusts in north and east London and Essex have been recruited to the study. These trusts will provide anonymised routine data for randomisation and outcomes analysis. The process evaluation will examine intervention implementation, acceptability, reach and possible causal pathways. The economic evaluation will use a cost-consequences analysis and decision model to evaluate the intervention. Targeted community engagement in the research process was a priority. DISCUSSION: Community REACH aims to increase early initiation of antenatal care using an intervention that is co-produced and delivered by local communities. This pragmatic cluster randomised controlled trial, with integrated process and economic evaluation, aims to rigorously assess the effectiveness of this public health intervention, which is particularly complex due to the required combination of standardisation with local flexibility. It will also answer questions about scalability and generalisability. TRIAL REGISTRATION: ISRCTN registry: registration number 63066975 . Registered on 18 August 2015.

A double-blind, randomized study of azithromycin compared to chloroquine for the treatment of Plasmodium vivax malaria in India.

Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection, but no controlled treatment studies have been performed. We conducted a double-blinded trial in P. vivax malaria in which patients were randomized to either azithromycin 1,000 mg q.d. x 3 or chloroquine 600 mg q.d. x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20. Eighty-five of 97 (88%) of those on azithromycin and 101 of 102 (99%) of those on chloroquine [difference 11%; 95% CI: -18, -4] were clinically cured at Day 7. The Day 28 results were similar [89% versus 99%, azithromycin versus chloroquine, respectively]. Parasitologic success was seen in 81 of 97 (84%) on azithromycin and 100 of 102 (98%) on chloroquine [difference 14%; 95% CI: -22, -6]. The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine (P < 0.001). Drug-related adverse events were seen in 13 of 98 (13%) on azithromycin and 24 of 102 (24%) on chloroquine (P = 0.062). Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin, but azithromycin was better tolerated. These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria, either alone as second-line treatment or in combination with other active therapies.

A multicenter study of azithromycin, alone and in combination with chloroquine, for the treatment of acute uncomplicated Plasmodium falciparum malaria in India.

BACKGROUND: Azithromycin has demonstrated in vitro and in vivo activity against Plasmodium falciparum, but small treatment studies have given mixed results. METHODS: Participants with fever and with both a blood smear and a rapid diagnostic test positive for falciparum malaria were randomly assigned to groups that were treated with either azithromycin or chloroquine or to matched groups receiving a placebo. After an interim analysis, open-label combination therapy with both drugs was initiated. RESULTS: At day 28, 5 (33%) of 15 participants in the azithromycin-treated group had remained free of fever, compared with 4 (27%) of 15 in the chloroquine-treated group. All subsequently enrolled participants then received combination therapy with azithromycin and chloroquine. In 61 (97%) of 67 participants, resolution of fever and parasitemia had occurred by day 7, and, through day 28, no clinical or parasitologic relapse had occurred in them. CONCLUSIONS: Resolution of parasitemia was inadequate with monotherapy with either azithromycin or chloroquine, but combination therapy provided substantially improved clinical and parasitologic outcomes. The combination of azithromycin and chloroquine may be an effective alternative treatment for falciparum malaria and deserves further study.