Clinical trial NCT02575755: A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant PNG Women
Official title: A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant Papua New Guinean Women
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pregnancy
Infections, Plasmodia
Drug Kinetics
Clinical Efficacy
Keywords: Azithromycin
Piperaquine
IPTp
Pharmacokinetics
Efficacy
Lead sponsor: Papua New Guinea Institute of Medical Research
Sponsor class: OTHER_GOV
Collaborators: name: The University of Western Australia
name: University of Melbourne
name: Malaria in Pregnancy Consortium
First posted: 2015-10-15
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy
timeFrame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Secondary outcomes:
measure: Pharmacokinetics - distribution, terminal elimination and absorption half-life(t1/2) of azithromycin and piperaquine
timeFrame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
measure: Pharmacokinetics - area under the plasma concentration versus time curve (AUC) of azithromycin and piperaquine
timeFrame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
measure: Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine
timeFrame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
measure: Pharmacokinetics - clearance (CL) of azithromycin and piperaquine
timeFrame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
measure: Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine
timeFrame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
measure: PCR adjusted 28 day cure
timeFrame: 28 days
measure: PCR adjusted 42 day cure
timeFrame: 42 days
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Other outcomes:
measure: Change in maternal hemoglobin over 28 days
timeFrame: 28 days
measure: Change in maternal weight over 28 days
timeFrame: 28 days
measure: Infant birth weight
timeFrame: Time of delivery
measure: Maternal parasitaemia
timeFrame: Time of delivery
measure: Placental parasitaemia
timeFrame: Time of delivery
measure: Cord blood parasitaemia
timeFrame: Time of delivery
measure: Maternal hemoglobin at delivery
timeFrame: Time of delivery
Locations:
city: Madang
country: Papua New Guinea
facility: Papua New Guinea Institute of Medical Research
state: Madang Province
Study officials:
References: