Efficacy,Safety and Tolerability of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Pregnancy in Ghana (DHAPPQ/MIP)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Kwame Nkrumah University of Science and Technology.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Joseph Osarfo, Kwame Nkrumah University of Science and Technology
ClinicalTrials.gov Identifier:
NCT01231113
First received: October 29, 2010
Last updated: April 19, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Pregnancy Complicated by Malaria as Antepartum Condition
Drug: artesunate-amodiaquine
Drug: Dihydroartemisinin-piperaquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Kwame Nkrumah University of Science and Technology:

Primary Outcome Measures:
  • PCR-corrected parasitological cure rates at days 28 and 42 [ Time Frame: 42-day follow-up ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • prevalence of birth defects [ Time Frame: assessment made 24-72 hours post-partum ] [ Designated as safety issue: Yes ]
    birth defects obvious on inspection

  • Comparative prevalence of adverse and serious adverse events [ Time Frame: three-monthly and at end of study ] [ Designated as safety issue: Yes ]
    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

  • pregnancy outcomes (spontaneous abortions, still births, preterm delivery, etc) [ Time Frame: quaterly from first recorded delivery and on completion ] [ Designated as safety issue: Yes ]
    data monitoring committee will assess generated data on the above and advice accordingly


Estimated Enrollment: 904
Study Start Date: July 2011
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: artesunate-amodiaquine arm Drug: artesunate-amodiaquine
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
Other Name: camosunate
Experimental: Dihydroartemisinin-piperaquine arm Drug: Dihydroartemisinin-piperaquine
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
Other Name: artekin

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.

  Eligibility

Ages Eligible for Study:   15 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01231113

Contacts
Contact: Joseph Osarfo, MBCHB, MPH +233244562908 josarfo@yahoo.co.uk

Locations
Ghana
St.Michael's Hospital, Pramso Recruiting
Kumasi, Ashanti Region, Ghana
Contact: Joseph Osarfo, MBCHB, MPH    +233244562908    josarfo@yahoo.co.uk   
Principal Investigator: Joseph Osarfo, MBCHB, MPH         
Sponsors and Collaborators
Kwame Nkrumah University of Science and Technology
Investigators
Principal Investigator: Joseph Osarfo, MBCHB, MPH Malaria Capacity Development Consortium-Ghana, Department of Community Health, School of Medical Science, Kwame Nkrumah University of Science and Technology
Study Director: Harry Tagbor, PhD Kwame Nkrumah University of Science and Technology
Study Director: Pascal Magnussen DBL-University of Copenhagen
  More Information

Additional Information:
No publications provided

Responsible Party: Joseph Osarfo, Principal Investigator, Kwame Nkrumah University of Science and Technology
ClinicalTrials.gov Identifier: NCT01231113     History of Changes
Other Study ID Numbers: version 8/DHAPPQ/MIP
Study First Received: October 29, 2010
Last Updated: April 19, 2012
Health Authority: Ghana: Committee on Human Research

Keywords provided by Kwame Nkrumah University of Science and Technology:
malaria,
pregnancy,
dihydroartemisinin-piperaquine,
efficacy,
safety,
Ghana

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Artesunate
Amodiaquine
Piperaquine
Dihydroartemisinin
Artemisinins
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials

ClinicalTrials.gov processed this record on September 18, 2014