Clinical Efficacy, Drug Kinetics, Infections, Plasmodia, Pregnancy
Conditions
Keywords
Azithromycin, Piperaquine, IPTp, Pharmacokinetics, Efficacy
Brief summary
Plasmodium falciparum parasitaemia in pregnancy is associated with maternal anaemia, low birth-weight and increased perinatal mortality. Whilst continuous prophylaxis is difficult to implement, intermittent presumptive treatment in pregnancy (IPTp) has proved to be practical and effective. In PNG, pregnant women currently receive IPTp using sulfadoxine-pyrimethamine, however, this therapy has the potential to be compromised by parasite resistance. The aim of the present trial is to assess the safety, tolerability, pharmacokinetics and efficacy of azithromycin (AZI) plus piperaquine (PQ) given as IPTp to pregnant Papua New Guinea women. The study will comprise of two sub-studies: (i) A safety, tolerability and pharmacokinetic study of AZI-PQ in pregnancy. (ii) A safety, tolerability and preliminary efficacy study of AZI-PQ in pregnancy.
Interventions
DRUGAzithromycin plus piperaquine phosphate
DRUGSulfadoxine-pyrimethamine
Sponsors
The University of Western Australia
University of Melbourne
Malaria in Pregnancy Consortium
Papua New Guinea Institute of Medical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* \>14 weeks and \<30 weeks gestation * No signs of severe malaria by World Health Organisation criteria * No significant concomitant disease (such as TB) * No prior history of an adverse reaction to AZI or PQP * No prior treatment with these drugs in the past 4 weeks * Can attend all follow-up visits * Provide informed consent
Exclusion criteria
* Have signs of severe malaria by WHO criteria * Significant concomitant disease such as TB as assessed by the attending clinician * A history/family history of sudden death or of congenital prolongation of the QTc interval * Any clinical condition known to prolong the QTc interval * A history of complicated pregnancies/deliveries * A prior history of an adverse reaction to AZI or PQP * Have taken these drugs in the past 4 weeks * Cannot attend any of the follow-up visits * Do not provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy | 42 days intensive follow-up, final end-point at 2 weeks post delivery | The efficacy of azithromycin plus piperaquine for the prevention of malaria infection during pregnancy will be investigated in 120 women. Women will be randomized to receive either (i) 3 daily doses of AZI plus PQ, or, (ii) single dose sulfadoxine-pyrimethamine Participants will be actively followed for a period of 42 days (1, 2, 3, 4, 7, 14, 21, 28 and 42 days after treatment). At each follow-up time point the participant will have a clinical examination, fundal height measurement and assessment of foetal lie, perform a symptoms questionnaire, blood film for malaria and other scheduled safety tests (eg. Hb, glucose, ultrasound). A single blood sample for pharmacokinetic analysis will be collected at Day 4. At delivery all participants and their babies will be assessed, including blood sample for Hb, glucose, blood spot for PCR, cord blood and maternal blood. Breast milk samples will be collected for 2 weeks (Day 1, 2, 3, 4, 7, 14) after the establishment of lactation. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics - area under the plasma concentration versus time curve (AUC) of azithromycin and piperaquine | 42 days intensive follow-up, final end-point at 2 weeks post delivery |
| Pharmacokinetics - distribution, terminal elimination and absorption half-life(t1/2) of azithromycin and piperaquine | 42 days intensive follow-up, final end-point at 2 weeks post delivery |
| Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine | 42 days intensive follow-up, final end-point at 2 weeks post delivery |
| Pharmacokinetics - clearance (CL) of azithromycin and piperaquine | 42 days intensive follow-up, final end-point at 2 weeks post delivery |
| Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine | 42 days intensive follow-up, final end-point at 2 weeks post delivery |
| PCR adjusted 28 day cure | 28 days |
| PCR adjusted 42 day cure | 42 days |
| Number of participants with adverse events as a measure of safety and tolerability | 42 days intensive follow-up, final end-point at 2 weeks post delivery |
Other
| Measure | Time frame |
|---|---|
| Cord blood parasitaemia | Time of delivery |
| Maternal hemoglobin at delivery | Time of delivery |
| Change in maternal hemoglobin over 28 days | 28 days |
| Change in maternal weight over 28 days | 28 days |
| Infant birth weight | Time of delivery |
| Placental parasitaemia | Time of delivery |
| Maternal parasitaemia | Time of delivery |
Countries
Papua New Guinea
Contacts
Primary ContactTimothy ME Davis, BMedSc MBBS DPhil FRACP MRCP
Backup ContactBrioni R Moore, BSc, PhD
Outcome results
None listed