Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants

ABSTRACT Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences (P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.)

A Comparative study of Extra-Amniotic Instillation of Ethacridine with Tablet Dinoprostone (PGE2) in Second Trimester Abortion Versus Ethacridine Alone

Aims: To study the efficacy of combination of extra-amniotic instillation of ethacridine with tablets Dinoprostone (PGE2) in second trimester abortion as compared to ethacridine alone. Methods: One hundred patients undergoing second trimester abortion were divided into two groups. Fifty patients received extra-amniotic ethacridine lactate 150 ml through Foley’s catheter (Ethacridine group) and the other 50 patients received 150 ml extra-amniotic ethacridine lactate mixed with a 0.5 mg of a crushed tablet of Dinoprostone through Foley’s catheter (Combination group). Both the groups were compared in respect to instillation-abortion interval, completeness of abortion and success rate. Results: The mean age, multiparity parity, and gestational age were comparable in both the groups. The instillation- abortion interval was significantly shorter in combination group as compared to ethacridine group (16.4±7.1 vs. 29.9 ±13.9 hours, p<0.001). Two patients in combination group had instillation abortion interval more than 48 hours as compared to 16 patients in ethacridine group(p<0.0005). Forty one patients (82%) in combination group had complete abortion as compared to 37 (74%) patients in ethacridine group. The success rate was 48/50(96%) in combination group as compared to 45/50 (90%) in ethacridine group. Conclusions: Addition of a 0.5 mg of crushed tablet of Dinoprostone in extra-amniotically instilled ethacridine lactate reduced the instillation-abortion interval significantly, increased the chances of complete abortion and increased the success rate. Nepal Journal of Obstetrics and Gynaecology / Vol 7 / No. 1 / Issue 13 / Jan- June, 2012 / 25-27 DOI: http://dx.doi.org/10.3126/njog.v7i1.8831