NCT02909712

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
201

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2016

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2016

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

September 5, 2016

Completed
16 days until next milestone

First Posted

Study publicly available on registry

September 21, 2016

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2020

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2020

Completed
Last Updated

February 2, 2021

Status Verified

January 1, 2020

Enrollment Period

3.3 years

First QC Date

September 5, 2016

Last Update Submit

February 1, 2021

Conditions

MalariaPregnancy MalariaCardiotoxicityCardiac SafetyParasitemia

Keywords

Sub-Saharan AfricaDihydroartemisininPiperaquineSulphadoxine-PyrimethamineAntimalarials

Outcome Measures

Primary Outcomes (2)

  • 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 on day 2 post-dose

  • 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 on day 7 post-dose

Secondary Outcomes (6)

  • 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.

    Measured on day 28 post-dose

  • 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

    Measured on day 7 post-dose

  • 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

    Measured on day 7 post-dose

  • 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

    Measured on day 7 post-dose

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

    Measured on day 28 post-dose

  • +1 more secondary outcomes

Study Arms (2)

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.

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.

Drug: dihydroartemisinin-piperaquine (DHA-PQP)

Interventions

sulfadoxine-pyrimethamine (SP)DRUG

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.

Also known as: Fansidar / Akacia Healthcare Ltd (South Africa)
sulfadoxine-pyrimethamine (SP)
dihydroartemisinin-piperaquine (DHA-PQP)DRUG

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.

Also known as: Eurartesim / Sigma-Tau (Italy)
dihydroartemisinin-piperaquine (DHA-PQP)

Eligibility Criteria

Age18 Years - 34 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.
  • 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).
  • +4 more criteria

You may not qualify if:

  • 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.
  • 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).
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Handeni District Hospital

Handeni, Tanga, Tanzania

Location

Related Publications (1)

  • 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.

    PMID: 16237860BACKGROUND

MeSH Terms

Conditions

MalariaCardiotoxicityParasitemia

Interventions

fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne DiseasesHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and InjuriesSepsisSystemic Inflammatory Response SyndromeInflammation

Study Officials

  • R. Matthew Chico, MPH, PhD

    London School of Hygiene and Tropical Medicine

    PRINCIPAL INVESTIGATOR

  • Jacklin Mosha, MBBS, MSc, PhD

    Kilimanjaro Christian Medical College

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 5, 2016

First Posted

September 21, 2016

Study Start

September 1, 2016

Primary Completion

January 1, 2020

Study Completion

February 1, 2020

Last Updated

February 2, 2021

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will not share

Results will be published in a peer-reviewed journal

Locations

TA(1)