NCT02575755

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
150

participants targeted

Target at P50-P75 for phase_4 pregnancy

Timeline
Completed

Started Oct 2012

Longer than P75 for phase_4 pregnancy

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2012

Completed
3 years until next milestone

First Submitted

Initial submission to the registry

October 8, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 15, 2015

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
Last Updated

October 15, 2015

Status Verified

October 1, 2015

Enrollment Period

3.8 years

First QC Date

October 8, 2015

Last Update Submit

October 14, 2015

Conditions

PregnancyInfections, PlasmodiaDrug KineticsClinical Efficacy

Keywords

AzithromycinPiperaquineIPTpPharmacokineticsEfficacy

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (8)

  • 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 - 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

  • Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine

    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

  • Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine

    42 days intensive follow-up, final end-point at 2 weeks post delivery

  • +3 more secondary outcomes

Other Outcomes (7)

  • Change in maternal hemoglobin over 28 days

    28 days

  • Change in maternal weight over 28 days

    28 days

  • Infant birth weight

    Time of delivery

  • +4 more other outcomes

Study Arms (3)

Efficacy Study: Azithromycin plus piperaquine

EXPERIMENTAL

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

Efficacy Study Control: National Standard Treatment

ACTIVE COMPARATOR

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

Pharmacokinetic Study: Azithromycin plus piperaquine

EXPERIMENTAL

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

Interventions

Azithromycin plus piperaquine phosphateDRUG
Also known as: Sandoz Azithromycin, Sigma-Tau Piperaquine tetraphosphate
Efficacy Study: Azithromycin plus piperaquinePharmacokinetic Study: Azithromycin plus piperaquine
Sulfadoxine-pyrimethamineDRUG
Efficacy Study Control: National Standard Treatment

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \>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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Papua New Guinea Institute of Medical Research

Madang, Madang Province, 511, Papua New Guinea

RECRUITING

MeSH Terms

Conditions

Infections

Interventions

Azithromycinpiperaquinefanasil, pyrimethamine drug combination

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Central Study Contacts

Timothy ME Davis, BMedSc MBBS DPhil FRACP MRCP

CONTACT

(+618) 9431 3229tim.davis@uwa.edu.au

Brioni R Moore, BSc, PhD

CONTACT

(+618) 6151 1172brioni.moore@uwa.edu.au

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 8, 2015

First Posted

October 15, 2015

Study Start

October 1, 2012

Primary Completion

July 1, 2016

Study Completion

October 1, 2016

Last Updated

October 15, 2015

Record last verified: 2015-10

Locations

PA(1)