The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial
Abstract Background Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased morta...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-018-2600-0 |
| _version_ | 1818611341577945088 |
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| author | Daniel J. Cooper Katherine Plewes Matthew J. Grigg Giri S. Rajahram Kim A. Piera Timothy William Mark D. Chatfield Tsin Wen Yeo Arjen M. Dondorp Nicholas M. Anstey Bridget E. Barber |
| author_facet | Daniel J. Cooper Katherine Plewes Matthew J. Grigg Giri S. Rajahram Kim A. Piera Timothy William Mark D. Chatfield Tsin Wen Yeo Arjen M. Dondorp Nicholas M. Anstey Bridget E. Barber |
| author_sort | Daniel J. Cooper |
| collection | DOAJ |
| description | Abstract Background Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI. The inexpensive and widely available drug paracetamol inhibits CFHb-induced lipid peroxidation via reduction of ferryl haem to the less toxic Fe3+ state, and has been shown to reduce oxidative damage and improve renal function in patients with sepsis complicated by haemolysis as well as in falciparum malaria. This study aims to assess the ability of regularly dosed paracetamol to reduce the incidence and severity of AKI in knowlesi malaria by attenuating haemolysis-induced oxidative damage. Methods PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel–Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity. Discussion Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases. Trial registration Clinicaltrials.gov, NCT03056391. Registered on 12 October 2016. |
| first_indexed | 2024-12-16T15:28:47Z |
| format | Article |
| id | doaj.art-f5d5ada53508498dad6b333aedf24ca8 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-16T15:28:47Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
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| series | Trials |
| spelling | doaj.art-f5d5ada53508498dad6b333aedf24ca82022-12-21T22:26:26ZengBMCTrials1745-62152018-04-0119111110.1186/s13063-018-2600-0The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trialDaniel J. Cooper0Katherine Plewes1Matthew J. Grigg2Giri S. Rajahram3Kim A. Piera4Timothy William5Mark D. Chatfield6Tsin Wen Yeo7Arjen M. Dondorp8Nicholas M. Anstey9Bridget E. Barber10Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityInfectious Diseases Society Sabah-Menzies School of Health Research Clinical Research UnitGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityInfectious Diseases Society Sabah-Menzies School of Health Research Clinical Research UnitGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol UniversityGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityAbstract Background Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI. The inexpensive and widely available drug paracetamol inhibits CFHb-induced lipid peroxidation via reduction of ferryl haem to the less toxic Fe3+ state, and has been shown to reduce oxidative damage and improve renal function in patients with sepsis complicated by haemolysis as well as in falciparum malaria. This study aims to assess the ability of regularly dosed paracetamol to reduce the incidence and severity of AKI in knowlesi malaria by attenuating haemolysis-induced oxidative damage. Methods PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel–Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity. Discussion Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases. Trial registration Clinicaltrials.gov, NCT03056391. Registered on 12 October 2016.http://link.springer.com/article/10.1186/s13063-018-2600-0MalariaPlasmodium knowlesiAcute kidney injuryParacetamol |
| spellingShingle | Daniel J. Cooper Katherine Plewes Matthew J. Grigg Giri S. Rajahram Kim A. Piera Timothy William Mark D. Chatfield Tsin Wen Yeo Arjen M. Dondorp Nicholas M. Anstey Bridget E. Barber The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial Trials Malaria Plasmodium knowlesi Acute kidney injury Paracetamol |
| title | The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial |
| title_full | The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial |
| title_fullStr | The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial |
| title_full_unstemmed | The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial |
| title_short | The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial |
| title_sort | effect of regularly dosed paracetamol versus no paracetamol on renal function in plasmodium knowlesi malaria packnow study protocol for a randomised controlled trial |
| topic | Malaria Plasmodium knowlesi Acute kidney injury Paracetamol |
| url | http://link.springer.com/article/10.1186/s13063-018-2600-0 |
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