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

Pregnancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02575755
• Other study ID #: MRAC10.53
• Status: Recruiting
• Phase: Phase 4
• First received: October 8, 2015
• Last updated: October 14, 2015
• Start date: October 2012
• Est. completion date: October 2016

Study information

• Verified date: October 2015
• Source: Papua New Guinea Institute of Medical Research
• Contact: Timothy ME Davis, BMedSc MBBS DPhil FRACP MRCP
• Phone: (+618) 9431 3229
• Email: tim.davis[@]uwa.edu.au
• Is FDA regulated: No
• Health authority: Papua New Guinea: Medical Society of Papua New Guinea
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Clinical Efficacy
• Drug Kinetics
• Infections, Plasmodia
• Malaria
• Pregnancy

Intervention

Drug:
• Azithromycin plus piperaquine phosphate

• Sulfadoxine-pyrimethamine

Locations

Country	Name	City	State
Papua New Guinea	Papua New Guinea Institute of Medical Research	Madang	Madang Province

Sponsors (4)

Lead Sponsor	Collaborator
Papua New Guinea Institute of Medical Research	Malaria in Pregnancy Consortium, The University of Western Australia, University of Melbourne

Country where clinical trial is conducted

Papua New Guinea, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in maternal hemoglobin over 28 days		28 days	No
Other	Change in maternal weight over 28 days		28 days	No
Other	Infant birth weight		Time of delivery	No
Other	Maternal parasitaemia		Time of delivery	No
Other	Placental parasitaemia		Time of delivery	No
Other	Cord blood parasitaemia		Time of delivery	No
Other	Maternal hemoglobin at delivery		Time of delivery	No
Primary	Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy	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.	42 days intensive follow-up, final end-point at 2 weeks post delivery	No
Secondary	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	No
Secondary	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	No
Secondary	Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine		42 days intensive follow-up, final end-point at 2 weeks post delivery	No
Secondary	Pharmacokinetics - clearance (CL) of azithromycin and piperaquine		42 days intensive follow-up, final end-point at 2 weeks post delivery	No
Secondary	Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine		42 days intensive follow-up, final end-point at 2 weeks post delivery	No
Secondary	PCR adjusted 28 day cure		28 days	No
Secondary	PCR adjusted 42 day cure		42 days	No
Secondary	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	No