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MalariaPhase 2NCT02909712

Cardiac Safety of Dihydroartemisinin-Piperaquine Amongst Pregnant Women in Tanzania

A Phase 2 study testing sulfadoxine-pyrimethamine (SP) and dihydroartemisinin-piperaquine (DHA-PQP) in people with Malaria and Pregnancy Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Tanzania.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Sulfadoxine-pyrimethamine (SP) is currently recommended by the World Health Organization for use as intermittent preventive treatment against malaria in pregnancy (IPTp) in areas of moderate to high malaria transmission. Read more about this study

Who is it for?
Ages 18 to 34 years, women onlyHealthy volunteers can take part
Conditions the study is for
Malaria, Pregnancy Malaria, Cardiotoxicity
What is being tested?
sulfadoxine-pyrimethamine (SP) and dihydroartemisinin-piperaquine (DHA-PQP)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
201 participants
Where
1 siteTanzania
Study dates
Sep 2016to Feb 2020
Phase
Phase 2
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 to 34 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Participant presents for antenatal care at the district hospital.
  • Participant is between 18 years and 34 years of age.
  • Participant currently lives within the pre-defined catchment area of the district hospital.
  • Participant will remain within the same area through to the post-partum visit.
  • Participant agrees to deliver her child at the district hospital.
  • Participant agrees to a post-partum visit at her residence or at the district hospital.
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  • Participant has no apparent severe infection or any condition that requires hospitalization.
  • Participant is not currently enrolled in another study.
  • Participant is not known to have heart disease or a known cardiac ailment.
  • Participant reports having taken no medication in the previous 28 days.
  • Participant reports having no known allergy to the study drugs or any sulphonamides.
  • Participant agrees to remain under observation for 3 hours at the district hospital and to abstain from food ingestion during the observation period in keeping with the European Medicines Agency product information for dosing with dihydroartemisinin-piperaquine.
  • Participant is willing to undergo all study procedures including sonography, ECG testing, and to provide blood samples for malaria microscopy and pharmacokinetic analysis.
  • Participant agrees to human immunodeficiency virus (HIV) testing regardless of prior results and no matter how recent.
  • Participant is not severely anaemic (haemoglobin concentration > 5g/dL).
  • Participant provides written consent.
  • Participant has an axillary temperature < 37.5 Celsius.
  • Participant is pregnant with a singleton determined by sonography.
  • Participant is between 16 and 35 weeks gestation determined by sonography.

Who cannot join

  • Participant is younger than 18 years of age and older than 35 years of age.
  • Participant does not currently live within the pre-defined catchment area of district hospital.
  • Participant will not remain within the same area through to the post-partum visit.
  • Participant does not agree to deliver her child at the district hospital.
  • Participant does not agree to a post-partum visit at her residence or at the district hospital.
  • Participant has a severe infection or any condition that requires hospitalization.
Show all 21Show fewer
  • Participant is currently enrolled in another study.
  • Participant is known to have heart disease or known cardiac ailment.
  • Participant reports having taken any medication in the previous 28 days.
  • Participant reports having an allergy to the study drugs or any sulphonamides.
  • Participant does not agree to abstain from food ingestion during the observation period after dosing.
  • Participant does not agree to remain under observation at the district hospital 3 hours after dosing has occurred.
  • Participant does not agree or is unwilling to undergo all study procedures including sonography, ECG testing, and to provide blood samples for malaria microscopy (and treatment group assignment) and pharmacokinetic analysis.
  • Participant does not agree to HIV testing or is diagnosed as HIV-positive during screening,
  • Participant is not severely anaemic (haemoglobin concentration > 5g/dL).
  • Participant does not provide written consent.
  • Participant has an axillary temperature > 37.5 Celsius or is symptomatic for malaria.
  • Participant is carrying a multiple pregnancy (e.g. twins).
  • Participant is between < 16 weeks and > 36 weeks gestation.
  • Participant has a QTc > 450 milliseconds.
  • Participant has a heart rate < 40 beats per minute.

Trial locations and contacts

1 site in 1 country.

Tanzania1 site

  • Handeni District Hospital

    Handeni, Tanga

Other trials in Tanzania

About this study

Sulfadoxine-pyrimethamine (SP) is currently recommended by the World Health Organization for use as intermittent preventive treatment against malaria in pregnancy (IPTp) in areas of moderate to high malaria transmission. However, in some locales malaria parasites have lost sensitivity to SP, compromising its protective effect. Dihydroartemisinin-piperaquine (DP) is a candidate replacement for SP. This trial is designed to confirm the cardio-safety of DP compared to SP amongst pregnant women in Tanzania.

Read the detailed description

The trial hypothesis is that DP will increase the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, a phenomenon referred to as QT prolongation, in the study population. However, if QT prolongation is observed, it is expected to be time-limited and of no clinical consequence.

The QT interval, measured in milliseconds (MS) will be corrected (QTc) to account for natural heart rate (HR) extremes. The Fridericia formula will also be used to correct (QTcF) for variation in cardio-contraction. As part of the electrocardiogram (ECG), the period from the beginning of the P wave to the beginning of the QRS complex (PR interval) will be measured, as well as the ST-segment which connects the QRS complex and the T wave.

Prolongation of the QT interval will be estimated when peak drug-concentrations are most likely to be found in the peripheral blood as measured using pharmacokinetic (PK) techniques. Polymerase chain reaction (PCR) methods will be used for genetic sequencing of molecular markers (A581G) associated with malaria parasite drug resistance to SP. The rapid diagnostic test (RDT) CareStart™ will be used to screen pregnant women attending antenatal care.

Being tested
sulfadoxine-pyrimethamine (SP), dihydroartemisinin-piperaquine (DHA-PQP)
Keywords
Sub-Saharan Africa, Dihydroartemisinin, Piperaquine, Sulphadoxine-Pyrimethamine, Antimalarials
Medical subject headings
Malaria, Cardiotoxicity, Parasitemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sulfadoxine-pyrimethamine (SP)Drug

    Also called Fansidar / Akacia Healthcare Ltd (South Africa)

    Women in Groups 1 and 2 will be provided the following SP regimen as directly observed therapy:

    3 tablets total of 500 mg sulphadoxine and 25 mg pyrimethamine; 1 day of dosing.

  • dihydroartemisinin-piperaquine (DHA-PQP)Drug

    Also called Eurartesim / Sigma-Tau (Italy)

    Women in Groups 3 and 4 will be provided the following DHA-PQP regimen as directly observed therapy 3 tablets of 40 mg dihydroartemisinin and 320 mg piperaquine daily; 9 tablets total; 3 days of dosing.

Study groups in NCT02909712
Study groupRoleWhat they receive
sulfadoxine-pyrimethamine (SP)Active comparator* Group 1 (50 CareStart™ RDT-positive women) * Group 2 (50 CareStart™ RDT-negative women) These 100 women will have an ECG exam, provide blood for microscopy and molecular analysis, and receive SP on day 0. On days 7, 14, 21, and 28 women will provide blood for microscopy and molecular analysis.
Receives: Drug: sulfadoxine-pyrimethamine (SP)
dihydroartemisinin-piperaquine (DHA-PQP)Experimental* Group 3 (50 CareStart™ RDT-positive women) * Group 4 (50 CareStart™ RDT-negative women) These 100 women will have an ECG exam, provide blood for microscopy, molecular, and PK analysis, and receive DHA-PQP day 0. On day 1, women will receive dose 2. On day 2, women will have an ECG exam, begin Holter monitoring, provide blood for PK analysis, and receive dose 3. Blood for PK analysis will be drawn at 4, 5, and 6 hours following dose 3. An ECG exam will be conducted during this period and, again, on day 7. On days 7, 14, 21, and 28, women will provide blood for microscopy and molecular analysis.
Receives: Drug: dihydroartemisinin-piperaquine (DHA-PQP)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean QTcF/QTcB change from baseline and proportion of pregnant women treated with DHA-PQP who experienced changes in RR, HR, PR, QRS, QT, QTcF and QTcB measurements from Day 0 pre-dose to Day 2 post-dose.

    Measured: Measured on day 2 post-dose

  2. Mean QTcF/QTcB change from baseline and proportion of pregnant women treated with DHA-PQP who experience changes in QT, QTcF and QTcB measurements from Day 0 pre-dose to Day 7.

    Measured: Measured on day 7 post-dose

Secondary outcomes (6)

  1. Proportion of pregnant women treated with DHA-PQP/SP with and without asymptomatic parasitaemia who experienced clinical symptoms that could be related with a cardiac arrhythmia.

    Clinical assessment

    Measured: Measured on day 28 post-dose

  2. Mean QTcF/QTcB change from baseline and proportion of pregnant women treated with SP who experience changes in QT, QTcF and QTcB measurements from Day 0 pre-dose to Day 7

    Electrocardiography

    Measured: Measured on day 7 post-dose

  3. Comparative analysis of the QT changes from Day 0 pre-dose to Day 7 post first dosing in pregnant women given DHA-PQP versus SP

    Electrocardiography

    Measured: Measured on day 7 post-dose

  4. Analysis of values and changes from baseline for the other electrocardiogram (ECG) parameters (RR, HR, PR, QRS) in pregnant women given DHA-PQP or SP

    Electrocardiography

    Measured: Measured on day 7 post-dose

  5. Adequate Parasitological Responses (APR) at Days 7, 14, 21 and 28 post-dose, PCR-Corrected and uncorrected

    Efficacy

    Measured: Measured on day 28 post-dose

  6. Proportion of participants in Groups 1-4 with parasites at Days 0, 7, 14, 21 and 28 that carry the 581G and/or K540E mutations associated with SP resistance

    Parasite resistance

    Measured: Measured on days 28 post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionJan 2020
  4. Study completionFeb 2020

Resources

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 2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
201 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02909712
Sponsor's protocol ID
ITDCZF16
Status last verified
Jan 2020
First submitted
5 Sep 2016
Last updated
2 Feb 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: Results will be published in a peer-reviewed journal

Publications

  • Food and Drug Administration, HHS. International Conference on Harmonisation; guidance on E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs; availability. Notice. Fed Regist. 2005 Oct 20;70(202):61134-5.

    PubMed 16237860

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sulfadoxine-pyrimethamine (SP) and dihydroartemisinin-piperaquine (DHA-PQP) in people with Malaria and Pregnancy Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Tanzania.

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 19 inclusion and 21 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 2 Feb 2021. 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 Tanzania. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Mean QTcF/QTcB change from baseline and proportion of pregnant women treated with DHA-PQP who experienced changes in RR, HR, PR, QRS, QT, QTcF and QTcB measurements from Day 0 pre-dose to Day 2 post-dose. (time frame: Measured on day 2 post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02909712, which also lists 1 linked publication.

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 2 Feb 2021.

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