PregnancyPhase 4NCT02575755
A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant PNG Women
A Phase 4 study testing Azithromycin plus piperaquine phosphate and Sulfadoxine-pyrimethamine in people with Pregnancy and Infections, Plasmodia, run by Papua New Guinea Institute of Medical Research at 1 site in Papua New Guinea.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pregnancy, Infections, Plasmodia, Drug Kinetics
- What is being tested?
- Azithromycin plus piperaquine phosphate and Sulfadoxine-pyrimethamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 sitePapua New Guinea
- Study dates
- Oct 2012to Oct 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- >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
Who cannot join
- 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
Show all 9Show fewer
- Have taken these drugs in the past 4 weeks
- Cannot attend any of the follow-up visits
- Do not provide informed consent
Trial locations and contacts
1 site in 1 country.
Papua New Guinea1 site, 1 recruiting
- Recruiting
Papua New Guinea Institute of Medical Research
Madang, Madang Province, 511
Brioni R Moore, BSc, PhD, (+61) 0466266334, brioni.moore@uwa.edu.au
Leanne J Robinson, BSc, PhD, MPH, (+675) 422 2909, robinson@wehi.edu.au
About this study
Official title: A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant Papua New Guinean Women
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.
- Conditions
- Pregnancy, Infections, Plasmodia, Drug Kinetics, Clinical Efficacy
- Being tested
- Azithromycin plus piperaquine phosphate, Sulfadoxine-pyrimethamine
- Keywords
- Azithromycin, Piperaquine, IPTp, Pharmacokinetics, Efficacy
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin plus piperaquine phosphateDrug
Also called Sandoz Azithromycin, Sigma-Tau Piperaquine tetraphosphate
Sulfadoxine-pyrimethamineDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Azithromycin plus piperaquine phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine
Measured: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Pharmacokinetics - clearance (CL) of azithromycin and piperaquine
Measured: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine
Measured: 42 days intensive follow-up, final end-point at 2 weeks post delivery
PCR adjusted 28 day cure
Measured: 28 days
PCR adjusted 42 day cure
Measured: 42 days
Number of participants with adverse events as a measure of safety and tolerability
Measured: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study startOct 2012
- Primary completionJul 2016 (estimated)
- Study completionOct 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Papua New Guinea Institute of Medical Research
- Sponsor type
- Other government
- Collaborators
- The University of Western Australia, University of Melbourne, Malaria in Pregnancy Consortium
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02575755
- Sponsor's protocol ID
- MRAC10.53
- Status last verified
- Oct 2015
- First submitted
- 8 Oct 2015
- Last updated
- 15 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant Papua New Guinean Women
- ClinicalTrials.gov ID
- NCT02575755
- Acronym / sponsor ID
- MRAC10.53
- Conditions
- Pregnancy, Infections, Plasmodia, Drug Kinetics, Clinical Efficacy
- Keywords
- Azithromycin, Piperaquine, IPTp, Pharmacokinetics, Efficacy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Papua New Guinea Institute of Medical ResearchOther government
- Collaborators
- The University of Western Australia, University of Melbourne, Malaria in Pregnancy Consortium
- Study start
- Oct 2012
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Oct 2016 (estimated)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Efficacy Study: Azithromycin plus piperaquine | Experimental | Drug: Azithromycin plus piperaquine phosphateAt 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 | Active comparator | Drug: Sulfadoxine-pyrimethamineAt 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 | Experimental | Drug: Azithromycin plus piperaquine phosphateAt 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- >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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin plus piperaquine phosphateAlso: Sandoz Azithromycin, Sigma-Tau Piperaquine tetraphosphate | Drug | Efficacy Study: Azithromycin plus piperaquine, Pharmacokinetic Study: Azithromycin plus piperaquine |
| Sulfadoxine-pyrimethamine | Drug | Efficacy Study Control: National Standard Treatment |
Primary outcome
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.
8 secondary outcomes
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
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
Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine
Time frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Pharmacokinetics - clearance (CL) of azithromycin and piperaquine
Time frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine
Time frame: 42 days intensive follow-up, final end-point at 2 weeks post delivery
PCR adjusted 28 day cure
Time frame: 28 days
PCR adjusted 42 day cure
Time frame: 42 days
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin plus piperaquine phosphate and Sulfadoxine-pyrimethamine in people with Pregnancy and Infections, Plasmodia, run by Papua New Guinea Institute of Medical Research at 1 site in Papua New Guinea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Papua New Guinea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Timothy ME Davis, BMedSc MBBS DPhil FRACP MRCP ((+618) 9431 3229, tim.davis@uwa.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2015.