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

Papua New Guinea Institute of Medical Research

Status and phase: Unknown; Phase 4

Conditions: Drug Kinetics; Infections, Plasmodia; Clinical Efficacy; Pregnancy

Treatments: Drug: Azithromycin plus piperaquine phosphate; Drug: Sulfadoxine-pyrimethamine

Study type: Interventional

Funder types: Other

Identifiers

NCT02575755

MRAC10.53

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 3 patient groups

Efficacy Study: Azithromycin plus piperaquine

Experimental group

Description:

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

Treatment:

Drug: Azithromycin plus piperaquine phosphate

Efficacy Study Control: National Standard Treatment

Active Comparator group

Description:

At baseline, participants receive a single dose of sulfadoxine-pyrimethamine comprising 1,500 mg of sulfadoxine and 75 mg pyrimethamine in tablet form

Treatment:

Drug: Sulfadoxine-pyrimethamine

Pharmacokinetic Study: Azithromycin plus piperaquine

Experimental group

Description:

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

Treatment:

Drug: Azithromycin plus piperaquine phosphate