Evidence map›Paper›PMID 30692558›Full record

ArticleScientific reports2019

Effects of Dihydroartemisinin-Piperaquine Phosphate and Artemether-Lumefantrine on QTc Interval Prolongation.

Christian Funck-Brentano, Antonella Bacchieri, Giovanni Valentini, Silvia Pace, Silva Tommasini, Pascal Voiriot, David Ubben, Stephan Duparc, Eric Evene, Mathieu Felices and 1 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01103830 (Phase I, Randomized, Parallel Group Study to Evaluate the Effect of Multiple Oral Doses of Eurartesim on the QT/QTc Interval Compared to Riamet, Placebo and Moxifloxacin in Healthy Male and Female Volunteers), which is not on this map. Cited by 11 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 3 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01103830 phase1completednot on this map

Phase I, Randomized, Parallel Group Study to Evaluate the Effect of Multiple Oral Doses of Eurartesim on the QT/QTc Interval Compared to Riamet, Placebo and Moxifloxacin in Healthy Male and Female Volunteers

TypeinterventionalSponsorsigma-tau i.f.r. S.p.A.Ran2010 to 2010Enrolled287ConditionsMalaria, FalciparumArmsEurartesim™, Riamet®, Placebo and finally Moxifloxacin
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 3 syntheses or guidelines pooled it, 24 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Christian Funck-BrentanoINSERM, CIC-1421 and UMR ICAN 1166, Sorbonne Université, Faculty of Medicine, AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, Institute of Cardiometabolism and Nutrition (ICAN), F-75013, Paris, France. christian.funck-brentano@aphp.fr.ORCID 0000-0003-0406-5189
Antonella BacchieriSigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, (Rome), Italy.
Giovanni ValentiniSigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, (Rome), Italy.
Silvia PaceSigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, (Rome), Italy.
Silva TommasiniSigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, (Rome), Italy.
Pascal VoiriotCardiabase, Nancy, France.
David UbbenMedicines for Malaria Venture, Geneva, Switzerland.
Stephan DuparcMedicines for Malaria Venture, Geneva, Switzerland.
Eric EveneSGS-Aster, Paris, France.
Mathieu FelicesPhinC development, Evry, France.
Marco CorsiSigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, (Rome), Italy.
Sigma Tau (Italy) · ITMedicines for Malaria Venture · CHInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

QT/QTc interval prolongation reflects delayed cardiac repolarization which can lead to Torsade de Pointes and sudden death. Many antimalarial drugs prolong QT/QTc interval. However, due to confounding factors in patients with malaria, the precise extent of this effect has been found to be highly variable among studies. We compared the effects of dihydroartemisinin-piperaquine phosphate (DHA-PQP) and artemether-lumefantrine (A-L) on QT interval duration in healthy volunteers. In this randomized, parallel groups, active moxifloxacin- and placebo-controlled study, prolongation of the QT/QTc interval following treatment with DHA-PQP in fasted and fed condition and A-L in fed state was investigated in healthy subjects (n = 287; Clinicaltrials.gov: NCT01103830). DHA-PQP resulted in significant mean (95% confidence interval (CI)) maximum increases in QTc Fridericia (QTcF) of 21.0 ms (15.7, 26.4) for DHA-PQP fasted, 35.9 ms (31.1, 40.6) for DHA-PQP high-fat/low-caloric and 46.0 ms (39.6, 52.3) for DHA-PQP high-fat/high-caloric breakfast. For A-L, the largest difference from baseline relative to placebo was 9.9 ms (95% CI: 6.8, 12.9). Increases in QTcF related to maximum plasma concentrations of piperaquine. Moxifloxacin demonstrated assay sensitivity. Increases in QTcF following DHA-PQP and A-L were clinically relevant. Food increased piperaquine exposure and QTcF interval prolongation emphasizing the need to administer DHA-PQP in the fasting state.

Identifiers

PMID30692558
PMCPMC6349839
OpenAlexW2911962834

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.