Pregnancy Complicated by Malaria as Antepartum Condition Clinical Trial
— DHAPPQ/MIPOfficial 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.
| Status | Completed |
| Enrollment | 417 |
| Est. completion date | February 2013 |
| Est. primary completion date | December 2012 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 15 Years to 45 Years |
| Eligibility |
Inclusion Criteria: - 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. vi) Haemoglobin = 7g/dl. Exclusion Criteria: - 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. iii) Known allergies to study medication. iv) Antimalarial treatment administered by a third party during the follow-up. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Ghana | St.Michael's Hospital, Pramso | Kumasi | Ashanti Region |
| Lead Sponsor | Collaborator |
|---|---|
| Kwame Nkrumah University of Science and Technology | Malaria Capacity Development Consortium |
Ghana,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 |
42-day follow-up | No |
| Secondary | prevalence of birth defects | birth defects obvious on inspection | assessment made 24-72 hours post-partum | Yes |
| Secondary | 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 | three-monthly and at end of study | Yes |
| Secondary | pregnancy outcomes (spontaneous abortions, still births, preterm delivery, etc) | data monitoring committee will assess generated data on the above and advice accordingly | quaterly from first recorded delivery and on completion | Yes |