SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02909712

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Cardio‑Safety of Dihydroartemisinin‑Piperaquine and Pharmacokinetics of Piperaquine Amongst Pregnant Women in Tanzania

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
MeSH: 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


1 A581G

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