Pregnancy Complicated by Malaria as Antepartum ConditionPhase 3DHAPPQ/MIPNCT01231113
Efficacy,Safety and Tolerability of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Pregnancy in Ghana
A Phase 3 study testing artesunate-amodiaquine and Dihydroartemisinin-piperaquine in people with Pregnancy Complicated by Malaria as Antepartum Condition, run by Kwame Nkrumah University of Science and Technology at 1 site in Ghana.
Trial summary
Malaria in pregnancy poses enormous public health challenges, contributing to significant maternal and infant deaths yearly. Adverse outcomes include maternal anaemia and low birthweight. Down regulation of cellular immunity increases pregnant women's susceptibility to malaria and mediate these adverse outcomes. Read more about this study
- Who is it for?
- Ages 15 to 45 years, women only
- Conditions the study is for
- Pregnancy Complicated by Malaria as Antepartum Condition
- What is being tested?
- artesunate-amodiaquine and Dihydroartemisinin-piperaquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 417 participants
- Where
- 1 siteGhana
- Study dates
- Jul 2011to Feb 2013
- Phase
- Phase 3
- 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 15 to 45 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- RDT positive + microscopy confirmed P. falciparum parasitaemia. ii) Informed consent. iii) Resident within the defined 15km radius of the study center. iv) No history of antimalarial treatment in the preceding two weeks. v) Assurance of adherence to study requirements, follow-up and delivery at the hospital.
- Haemoglobin ≥ 7g/dl.
Who cannot join
- i) Confirmed multiple gestation. ii) Severe malaria or disease likely to influence pregnancy outcome eg renal/ cardiac disease, diabetes mellitus, known pregnancy induced hypertension, known human immunodeficiency virus infection.
- Known allergies to study medication. iv) Antimalarial treatment administered by a third party during the follow-up.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy, Safety and Tolerability of Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Falciparum Malaria in Pregnancy: an Open-label, Randomised Controlled, Non-inferiority Trial
Malaria in pregnancy poses enormous public health challenges, contributing to significant maternal and infant deaths yearly. Adverse outcomes include maternal anaemia and low birthweight. Down regulation of cellular immunity increases pregnant women's susceptibility to malaria and mediate these adverse outcomes.
The World Health Organization recommends treatment with artemisinin-combination therapy. Ghana uses quinine for malaria in first trimester pregnancies while artesunate-amodiaquine (AS-AQ) and quinine again are used in later trimesters. Recent amendments added artesunate-lumefantrine and dihydroartemisinin-piperaquine (DHA-PPQ) to the antimalarials used in the country. A high degree of safety and efficacy of DHA-PPQ is documented in several studies. DHA-PPQ, though not specified for use in pregnancy as of now, is accessible and available following its inclusion in the national malaria guidelines and may inadvertently be used to treat malaria in pregnancy. Paucity of data on DHA-PPQ use in pregnancy makes it pertinent to study its safety, tolerability and efficacy in pregnancy.
We propose an open label, randomized controlled non-inferiority comparison of DHA-PPQ and AS-AQ for treatment of uncomplicated malaria in pregnancy in second and third trimesters to assess safety, tolerability and efficacy of DHA-PPQ. Outcomes of interest include PCR-corrected cure rates at days 28 and 42, maternal haemoglobin levels at days 14 and 42, prevalence of congenital abnormalities and pregnancy wastage. Proportions and percentages will be described at 95% Confidence Intervals and compared using chi-square tests. Parametric and non-parametric tests of significance will be applied as appropriate to determine significance of differences in outcomes between the treatment groups.
Read the detailed description
Pregnant women of all ages, gravidity and with gestational ages 16-30 weeks, living within 15 km of the study center and presenting for antenatal care or diagnosed with uncomplicated malaria will be screened with P.falciparum rapid diagnostic test kits after obtaining consent. Those testing positive will have blood film microscopy done and only those with positive blood film microscopy will be recruited to participate in the study. Participants will be randomized to receive either dihydroartemisinin-piperaquine at an estimated total dosing of 6.75mg/kg of dihydroartemisinin and 55mg/kg of piperaquine for 3 days rounded to the nearest half tablet) or artesunate-amodiaquine(artesunate 4mg/kg and amodiaquine 10mg/kg in two twelve hourly doses daily for 3 days) after giving informed consent and a physical examination. This will be followed by home visits on days 1, 3, 7, 14, 28 and 42 post-treatment to assess occurrence of adverse events and to obtain blood samples for microscopy, filter paper blots for PCR analysis and haematology. The mentioned laboratory investigations will also be conducted at recruitment.
Participants will be followed up to delivery and 6 weeks post-partum to gather data on maternal peripheral and placental parasitaemia, cord parasitaemia, maternal haemoglobin levels, low birth weights, stillbirths, preterm deliveries, neonatal jaundice, birth defects and infant deaths.
- Being tested
- artesunate-amodiaquine, Dihydroartemisinin-piperaquine
- Keywords
- malaria,, pregnancy,, dihydroartemisinin-piperaquine,, efficacy,, safety,, Ghana
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
artesunate-amodiaquineDrug
Also called camosunate
The 452 pregnant women in this arm will receive artesunate-amodiaquine tablets(artesunate 4mg/kg and amodiaquine 10mg/kg in twelve hourly doses over 3 days
Dihydroartemisinin-piperaquineDrug
Also called artekin
a fixed-dose combination to be administered to the other 452 pregnant women in this arm at an estimated total dosing of 6.75mg/kg dihydroartemisinin and 55mg/kg piperaquine over 3 days
| Study group | Role | What they receive |
|---|---|---|
| artesunate-amodiaquine arm | Active comparator | A co-blistered pack of amodiaquine and artesunate.The 452 pregnant women in this arm will receive artesunate-amodiaquine tablets(artesunate 4mg/kg and amodiaquine 10mg/kg in twelve hourly doses over 3 days Receives: Drug: artesunate-amodiaquine |
| Dihydroartemisinin-piperaquine arm | Experimental | a fixed-dose combination to be administered to the other 452 pregnant women in this arm at an estimated total dosing of 6.75mg/kg dihydroartemisinin and 55mg/kg piperaquine over 3 days Receives: Drug: Dihydroartemisinin-piperaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PCR-corrected parasitological cure rates at days 28 and 42
Only eligible subjects with positive falciparum rapid diagnostic test results and positive blood films on microscopy will be recruited. Filter paper blots will be prepared at recruitment as well.
Blood films and filter paper blots will be repeated on days 3,7,14,28 and 42 post-first dose of treatment.
PCR analysis will be conducted on only those follow-ups with positive blood films
Measured: 42-day follow-up
Secondary outcomes (3)
prevalence of birth defects
birth defects obvious on inspection
Measured: assessment made 24-72 hours post-partum
Comparative prevalence of adverse and serious adverse events
the data monitoring committee will assess adverse events data quarterly and advice accordingly. Where there is no justification to stop the study before completion, the final assessments will done on study completion
Measured: three-monthly and at end of study
pregnancy outcomes (spontaneous abortions, still births, preterm delivery, etc)
data monitoring committee will assess generated data on the above and advice accordingly
Measured: quaterly from first recorded delivery and on completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2010 (estimated)
- Study startJul 2011
- Primary completionDec 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pregnancy Complicated by Malaria as Antepartum ConditionStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 417 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kwame Nkrumah University of Science and Technology
- Sponsor type
- University, hospital or other
- Collaborators
- Malaria Capacity Development Consortium
- Responsible party
- Principal investigator, Joseph Osarfo, Kwame Nkrumah University of Science and Technology
- Investigators
- Joseph Osarfo, MBCHB, MPH, Principal investigator, Malaria Capacity Development Consortium-Ghana, Department of Community Health, School of Medical Science, Kwame Nkrumah University of Science and TechnologyHarry Tagbor, PhD, Study director, Kwame Nkrumah University of Science and TechnologyPascal Magnussen, Study director, DBL-University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01231113
- Sponsor's protocol ID
- version 8/DHAPPQ/MIP
- Acronym
- DHAPPQ/MIP
- Status last verified
- Feb 2016
- First submitted
- 29 Oct 2010
- Last updated
- 24 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety and Tolerability of Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Falciparum Malaria in Pregnancy: an Open-label, Randomised Controlled, Non-inferiority Trial
- ClinicalTrials.gov ID
- NCT01231113
- Acronym / sponsor ID
- DHAPPQ/MIP / version 8/DHAPPQ/MIP
- Keywords
- malaria,, pregnancy,, dihydroartemisinin-piperaquine,, efficacy,, safety,, Ghana
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 417 participants (actual)
- Lead sponsor
- Kwame Nkrumah University of Science and TechnologyUniversity, hospital or other
- Collaborators
- Malaria Capacity Development Consortium
- Study start
- Jul 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 1 Nov 2010 (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.
Malaria in pregnancy poses enormous public health challenges, contributing to significant maternal and infant deaths yearly. Adverse outcomes include maternal anaemia and low birthweight. Down regulation of cellular immunity increases pregnant women's susceptibility to malaria and mediate these adverse outcomes.
The World Health Organization recommends treatment with artemisinin-combination therapy. Ghana uses quinine for malaria in first trimester pregnancies while artesunate-amodiaquine (AS-AQ) and quinine again are used in later trimesters. Recent amendments added artesunate-lumefantrine and dihydroartemisinin-piperaquine (DHA-PPQ) to the antimalarials used in the country. A high degree of safety and efficacy of DHA-PPQ is documented in several studies. DHA-PPQ, though not specified for use in pregnancy as of now, is accessible and available following its inclusion in the national malaria guidelines and may inadvertently be used to treat malaria in pregnancy. Paucity of data on DHA-PPQ use in pregnancy makes it pertinent to study its safety, tolerability and efficacy in pregnancy.
We propose an open label, randomized controlled non-inferiority comparison of DHA-PPQ and AS-AQ for treatment of uncomplicated malaria in pregnancy in second and third trimesters to assess safety, tolerability and efficacy of DHA-PPQ. Outcomes of interest include PCR-corrected cure rates at days 28 and 42, maternal haemoglobin levels at days 14 and 42, prevalence of congenital abnormalities and pregnancy wastage. Proportions and percentages will be described at 95% Confidence Intervals and compared using chi-square tests. Parametric and non-parametric tests of significance will be applied as appropriate to determine significance of differences in outcomes between the treatment groups.
Detailed description
Pregnant women of all ages, gravidity and with gestational ages 16-30 weeks, living within 15 km of the study center and presenting for antenatal care or diagnosed with uncomplicated malaria will be screened with P.falciparum rapid diagnostic test kits after obtaining consent. Those testing positive will have blood film microscopy done and only those with positive blood film microscopy will be recruited to participate in the study. Participants will be randomized to receive either dihydroartemisinin-piperaquine at an estimated total dosing of 6.75mg/kg of dihydroartemisinin and 55mg/kg of piperaquine for 3 days rounded to the nearest half tablet) or artesunate-amodiaquine(artesunate 4mg/kg and amodiaquine 10mg/kg in two twelve hourly doses daily for 3 days) after giving informed consent and a physical examination. This will be followed by home visits on days 1, 3, 7, 14, 28 and 42 post-treatment to assess occurrence of adverse events and to obtain blood samples for microscopy, filter paper blots for PCR analysis and haematology. The mentioned laboratory investigations will also be conducted at recruitment.
Participants will be followed up to delivery and 6 weeks post-partum to gather data on maternal peripheral and placental parasitaemia, cord parasitaemia, maternal haemoglobin levels, low birth weights, stillbirths, preterm deliveries, neonatal jaundice, birth defects and infant deaths.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| artesunate-amodiaquine arm | Active comparator | Drug: artesunate-amodiaquineA co-blistered pack of amodiaquine and artesunate.The 452 pregnant women in this arm will receive artesunate-amodiaquine tablets(artesunate 4mg/kg and amodiaquine 10mg/kg in twelve hourly doses over 3 days |
| Dihydroartemisinin-piperaquine arm | Experimental | Drug: Dihydroartemisinin-piperaquinea fixed-dose combination to be administered to the other 452 pregnant women in this arm at an estimated total dosing of 6.75mg/kg dihydroartemisinin and 55mg/kg piperaquine over 3 days |
Who may qualify
- Ages
- 15 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- RDT positive + microscopy confirmed P. falciparum parasitaemia. ii) Informed consent. iii) Resident within the defined 15km radius of the study center. iv) No history of antimalarial treatment in the preceding two weeks. v) Assurance of adherence to study requirements, follow-up and delivery at the hospital.
- Haemoglobin ≥ 7g/dl.
Key exclusion criteria (2 listed)
- i) Confirmed multiple gestation. ii) Severe malaria or disease likely to influence pregnancy outcome eg renal/ cardiac disease, diabetes mellitus, known pregnancy induced hypertension, known human immunodeficiency virus infection.
- Known allergies to study medication. iv) Antimalarial treatment administered by a third party during the follow-up.
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 |
|---|---|---|
| artesunate-amodiaquineAlso: camosunateThe 452 pregnant women in this arm will receive artesunate-amodiaquine tablets(artesunate 4mg/kg and amodiaquine 10mg/kg in twelve hourly doses over 3 days | Drug | artesunate-amodiaquine arm |
| Dihydroartemisinin-piperaquineAlso: artekina fixed-dose combination to be administered to the other 452 pregnant women in this arm at an estimated total dosing of 6.75mg/kg dihydroartemisinin and 55mg/kg piperaquine over 3 days | Drug | Dihydroartemisinin-piperaquine arm |
Primary outcome
PCR-corrected parasitological cure rates at days 28 and 42
Time frame: 42-day follow-up
Only eligible subjects with positive falciparum rapid diagnostic test results and positive blood films on microscopy will be recruited. Filter paper blots will be prepared at recruitment as well. Blood films and filter paper blots will be repeated on days 3,7,14,28 and 42 post-first dose of treatment. PCR analysis will be conducted on only those follow-ups with positive blood films
3 secondary outcomes
prevalence of birth defects
Time frame: assessment made 24-72 hours post-partum
Comparative prevalence of adverse and serious adverse events
Time frame: three-monthly and at end of study
pregnancy outcomes (spontaneous abortions, still births, preterm delivery, etc)
Time frame: quaterly from first recorded delivery and on completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
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.
Joseph Osarfo, MBCHB, MPH principal investigator
Malaria Capacity Development Consortium-Ghana, Department of Community Health, School of Medical Science, Kwame Nkrumah University of Science and Technology
Harry Tagbor, PhD study director
Kwame Nkrumah University of Science and Technology
Pascal Magnussen study director
DBL-University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing artesunate-amodiaquine and Dihydroartemisinin-piperaquine in people with Pregnancy Complicated by Malaria as Antepartum Condition, run by Kwame Nkrumah University of Science and Technology at 1 site in Ghana.
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 2 inclusion and 2 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: finished, as of the sponsor's last update on 24 Feb 2016. 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 Ghana. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PCR-corrected parasitological cure rates at days 28 and 42 (time frame: 42-day follow-up). 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 24 Feb 2016.