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

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ClinicalTrials.gov Identifier: NCT02575755
Recruitment Status : Unknown
Verified October 2015 by Papua New Guinea Institute of Medical Research.
Recruitment status was:  Recruiting
First Posted : October 15, 2015
Last Update Posted : October 15, 2015
Sponsor:
Collaborators:
The University of Western Australia
University of Melbourne
Malaria in Pregnancy Consortium
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Pregnancy Infections, Plasmodia Drug Kinetics Clinical Efficacy Drug: Azithromycin plus piperaquine phosphate Drug: Sulfadoxine-pyrimethamine Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant Papua New Guinean Women
Study Start Date : October 2012
Estimated Primary Completion Date : July 2016
Estimated Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Efficacy Study: Azithromycin plus piperaquine
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
Drug: Azithromycin plus piperaquine phosphate
Other Names:
  • Sandoz Azithromycin
  • Sigma-Tau Piperaquine tetraphosphate

Active Comparator: Efficacy Study Control: National Standard Treatment
At baseline, participants receive a single dose of sulfadoxine-pyrimethamine comprising 1,500 mg of sulfadoxine and 75 mg pyrimethamine in tablet form
Drug: Sulfadoxine-pyrimethamine
Experimental: Pharmacokinetic Study: Azithromycin plus piperaquine
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
Drug: Azithromycin plus piperaquine phosphate
Other Names:
  • Sandoz Azithromycin
  • Sigma-Tau Piperaquine tetraphosphate




Primary Outcome Measures :
  1. Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy [ Time Frame: 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 :
  1. Pharmacokinetics - distribution, terminal elimination and absorption half-life(t1/2) of azithromycin and piperaquine [ Time Frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery ]
  2. Pharmacokinetics - area under the plasma concentration versus time curve (AUC) of azithromycin and piperaquine [ Time Frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery ]
  3. Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine [ Time Frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery ]
  4. Pharmacokinetics - clearance (CL) of azithromycin and piperaquine [ Time Frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery ]
  5. Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine [ Time Frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery ]
  6. PCR adjusted 28 day cure [ Time Frame: 28 days ]
  7. PCR adjusted 42 day cure [ Time Frame: 42 days ]
  8. Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery ]

Other Outcome Measures:
  1. Change in maternal hemoglobin over 28 days [ Time Frame: 28 days ]
  2. Change in maternal weight over 28 days [ Time Frame: 28 days ]
  3. Infant birth weight [ Time Frame: Time of delivery ]
  4. Maternal parasitaemia [ Time Frame: Time of delivery ]
  5. Placental parasitaemia [ Time Frame: Time of delivery ]
  6. Cord blood parasitaemia [ Time Frame: Time of delivery ]
  7. Maternal hemoglobin at delivery [ Time Frame: Time of delivery ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02575755


Contacts
Contact: Timothy ME Davis, BMedSc MBBS DPhil FRACP MRCP (+618) 9431 3229 tim.davis@uwa.edu.au
Contact: Brioni R Moore, BSc, PhD (+618) 6151 1172 brioni.moore@uwa.edu.au

Locations
Papua New Guinea
Papua New Guinea Institute of Medical Research Recruiting
Madang, Madang Province, Papua New Guinea, 511
Contact: Brioni R Moore, BSc, PhD    (+61) 0466266334    brioni.moore@uwa.edu.au   
Contact: Leanne J Robinson, BSc, PhD, MPH    (+675) 422 2909    robinson@wehi.edu.au   
Sponsors and Collaborators
Papua New Guinea Institute of Medical Research
The University of Western Australia
University of Melbourne
Malaria in Pregnancy Consortium

Responsible Party: Papua New Guinea Institute of Medical Research
ClinicalTrials.gov Identifier: NCT02575755     History of Changes
Other Study ID Numbers: MRAC10.53
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: October 15, 2015
Last Verified: October 2015

Keywords provided by Papua New Guinea Institute of Medical Research:
Azithromycin
Piperaquine
IPTp
Pharmacokinetics
Efficacy

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Pyrimethamine
Piperaquine
Sulfadoxine
Fanasil, pyrimethamine drug combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents