SNPMiner Trials: Clinical Trial Report
Report for Clinical Trial NCT02909712
Developed by Shray Alag, 2019.
SNP Clinical Trial Gene
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.
NCT02909712 Malaria Pregnancy Cardiotoxicity Parasitemia
2 Interventions
Name: sulfadoxine-pyrimethamine (SP)
Description: 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.Type: Drug
sulfadoxine-pyrimethamine (SP)
Name: dihydroartemisinin-piperaquine (DHA-PQP)
Description: 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.Type: Drug
dihydroartemisinin-piperaquine (DHA-PQP)
Primary Outcomes
Measure: Proportion of participants in Groups 3-4 with an absolute QTc of > 500 milliseconds
Time: Measured on day 7 post-dose
Secondary Outcomes
Measure: Proportion of participants in Groups 1-2 with an absolute QTc of > 500 milliseconds
Time: Measured on day 0
Measure: Proportion of participants in Groups 1-2 with an absolute QTc of > 480 milliseconds
Time: Measured on day 0
Measure: Proportion of participants in Groups 1-2 with an absolute QTc of > 460 milliseconds
Time: Measured on day 0
Measure: Proportion of participants in Groups 3-4 with an absolute QTc of > 500 milliseconds
Time: Measured on day 2
Measure: Proportion of participants in Groups 3-4 with an absolute QTc of > 480 milliseconds
Time: Measured on day 2
Measure: Proportion of participants in Groups 3-4 with an absolute QTc of > 450 milliseconds
Time: Measured on day 2
Measure: Incidence of participants in Groups 1-4 with QTcF prolongation > 500 milliseconds.
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants in Groups 1-4 with QTcF deviation from baseline > 60 milliseconds
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants in Groups 1-4 with ventricular arrhythmia captured on ECG recording and/or suspected by a clinical event as palpitation, dizziness, syncope, convulsion, or sudden death
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with mean heart rate < 40 beats per minute
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with mean heart rate > 130 beats per minute
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with PR interval > 210 milliseconds
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with PR interval > 220 milliseconds
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with QRS interval > 110 milliseconds
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with QRS interval > 120 milliseconds
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with change in QTcF from baseline > 60 milliseconds + Absolute QTc > 480 milliseconds (QTcF refers to the QT interval that has been corrected using the Fridericia formula)
Time: Measured on days 2 and 7
Measure: Proportion of participants in Groups 1-4 with QTcF > 480 milliseconds and > 500 milliseconds (QTcF refers to the QT interval that has been corrected using the Fridericia formula)
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 3-4 with change in QTcF between day 0 pre-dose, day 2 post dose at peak > 60 milliseconds, and day 7 (QTcF refers to the QT interval that has been corrected using the Fridericia formula)
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-4 with arrhythmias
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants in Groups 3-4 with sinus pause / arrest > 3.0 seconds
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants in Groups 3-4 with 2nd degree atrioventricular block (Mobitz 2)
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants in Groups 3-4 with 3rd degree atrioventricular block
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants with ventricular tachycardia
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants with torsades de pointes
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants with ventricular fibrillation
Time: Measured on days 0, 2 and 7
Measure: Mean piperaquine absorption at maximum observed concentrations (Cmax) in Groups 3-4
Time: Measured on day 2
Measure: Incidence of participants who experience myocardial ischemia defined as: • ST-segment deviations ≥ 1 millimetre 80 millisecond after J-point, or • New Q-waves, or T-wave inversion
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants who experience morphological changes of the T-wave
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants who experience pathological U-wave
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants who experience sinus pause or arrest > 3.0 seconds
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants who experience 2nd degree atrioventricular block (Mobitz 2)
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants who experience 3rd degree atrioventricular block
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants who experience complete right bundle branch block
Time: Measured on days 0, 2 and 7
Measure: Incidence of participants who experience complete left bundle branch block
Time: Measured on days 0, 2 and 7
Measure: Proportion of participants in Groups 1-2 with and without parasitaemia at day 0 administered SP, who are aparasitaemic at day 7, day 14 and day 28, uncorrected and corrected by PCR methods
Time: Days 0, 7, 14, and 28
Measure: Proportion of participants in Groups 3-4 administered dihydroartemisinin‑piperaquine with and without parasitaemia at day 0, who are aparasitaemic at day 7, day 14 and day 28, uncorrected and corrected by PCR methods
Time: Days 0, 7, 14, and 28
Measure: Proportion of participants in Groups 1-4 with parasites that carry the A581G mutation and others biomarkers associated with SP resistance.
Time: Day 0
Purpose: Basic Science
Allocation: Randomized
Parallel Assignment
There is one SNP
SNPs
Proportion of participants in Groups 1-4 with parasites that carry the A581G mutation and others biomarkers associated with SP resistance.. null. --- A581G ---
Polymerase chain reaction (PCR) methods will be used for genetic sequencing of molecular
markers (A581G) associated with malaria parasite drug resistance to SP. --- A581G ---
HPO Nodes