A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant PNG Women

Phase 4

• Conditions: Pregnancy; Infections, Plasmodia; Drug Kinetics; Clinical Efficacy
• Interventions: Drug: Azithromycin plus piperaquine phosphate; Drug: Sulfadoxine-pyrimethamine

• Registration Number: NCT02575755
• Lead Sponsor: Papua New Guinea Institute of Medical Research

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10
• Status Verified: 2015-10
• Study First Submitted: 2015-10-08
• Study First Submitted QC: 2015-10-14
• Last Update Submitted: 2015-10-14
• Study First Posted: 2015-10-15
• Last Update Posted: 2015-10-15
• Primary Completion: 2016-07
• Study Completion: 2016-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 150

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Efficacy Study: Azithromycin plus piperaquine	Azithromycin plus piperaquine phosphate	At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets
Efficacy Study Control: National Standard Treatment	Sulfadoxine-pyrimethamine	At baseline, participants receive a single dose of sulfadoxine-pyrimethamine comprising 1,500 mg of sulfadoxine and 75 mg pyrimethamine in tablet form
Pharmacokinetic Study: Azithromycin plus piperaquine	Azithromycin plus piperaquine phosphate	At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine	42 days intensive follow-up, final end-point at 2 weeks post delivery
PCR adjusted 42 day cure	42 days
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 - 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
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
Pharmacokinetics - clearance (CL) of azithromycin and piperaquine	42 days intensive follow-up, final end-point at 2 weeks post delivery
PCR adjusted 28 day cure	28 days

Trial Locations

Locations (1)

Papua New Guinea Institute of Medical Research; 🇵🇬 Madang, Madang Province, Papua New Guinea