Dataset Information

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial.

ABSTRACT:

Background

Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome.

Methods

This is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles.

Discussion

When complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement.

Trial registration

International Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.

SUBMITTER: Siriwardena AK

PROVIDER: S-EPMC6664733 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial.

Siriwardena Ajith K AK Jegatheeswaran Santhalingam S Mason James M JM Baltatzis Minas M Chan Anthony A Sheen Aali J AJ O'Reilly Derek D Jamdar Saurabh S Deshpande Rahul R de Liguori Carino Nicola N Satyadas Thomas T Qamruddin Ahmed A Hayden Katharine K Parker Michael J MJ Butler John J Rajai Azita A McIntyre Ben B

Trials 20190729 1

<h4>Background</h4>Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm f ...[more]

PMID: 31358032

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Project description:IntroductionAcute pancreatitis is an inflammatory disease of the pancreas with high risk of developing multiorgan failure and death. There are no effective pharmacological interventions used in current clinical practice. Maintaining fluid and electrolyte balance is the mainstay of supportive management. Goal-directed fluid therapy (GDFT) has been shown to decrease morbidity and mortality in surgical conditions with systemic inflammatory response. There is currently no randomised controlled trial (RCT) investigating the role of GDFT based on cardiac output parameters in patients with acute pancreatitis in the ward setting. A feasibility trial was designed to determine patient and clinician support for recruitment into an RCT of ward-based GDFT in acute pancreatitis, adherence to a GDFT protocol, safety, participant withdrawal, and to determine appropriate endpoints for a subsequent larger trial to evaluate efficacy.Methods and analysisThe GDFT in Acute Pancreatitis trial is a prospective two-centre feasibility RCT. Eligible adults admitted with new onset of acute pancreatitis will be enrolled and randomised into ward-based GDFT (n=25) or standard fluid therapy (n=25) within 6 hours from the diagnosis and continuing for the following 48 hours. Cardiac output parameters will be monitored with a non-invasive device (Cheetah NICOM; Cheetah Medical). The intervention group will consist of a protocolised GDFT approach consisting of stroke volume optimisation with crystalloid fluid boluses, while the control group will receive standard care fluid therapy as advised by the clinical team. The primary endpoint is feasibility. Secondary endpoints will include safety of the intervention, complications, mortality, admission to intensive care unit, cost and quality of life.Ethics and disseminationEthics approval was granted by the London Central Research Ethics Committee (17/LO/1235, project ID: 221872). The results of this trial will be presented to international conference with interest in general surgery and acute care and published in a peer-reviewed journal.Trial registration numberISRCTN36077283.

Project description:BACKGROUND:Despite evidence from clinical trials that intravenous (IV) thrombolysis is a cost-effective treatment for selected acute ischaemic stroke patients, there remain large variations in the rate of IV thrombolysis delivery between stroke services. This study is evaluating whether an enhanced care pathway delivered by paramedics (the Paramedic Acute Stroke Treatment Assessment (PASTA)) could increase the number of patients who receive IV thrombolysis treatment. METHODS:Study design: Cluster randomised trial with economic analysis and parallel process evaluation. SETTING:National Health Service ambulance services, emergency departments and hyper-acute stroke units within three geographical regions of England and Wales. Randomisation: Ambulance stations within each region are the units of randomisation. According to station allocation, paramedics based at a station deliver the PASTA pathway (intervention) or continue with standard stroke care (control). Study intervention: The PASTA pathway includes structured pre-hospital information collection, prompted pre-notification, structured handover of information in hospital and assistance with simple tasks during the initial hospital assessment. Study-trained intervention group paramedics deliver this pathway to adults within 4 h of suspected stroke onset. Study control: Standard stroke care according to national and local guidelines for the pre-hospital and hospital assessment of suspected stroke. PARTICIPANTS:Participants enrolled in the study are adults with confirmed stroke who were assessed by a study paramedic within 4 h of symptom onset. PRIMARY OUTCOME:Proportion of participants receiving IV thrombolysis. SAMPLE SIZE:1297 participants provide 90% power to detect a 10% difference in the proportion of patients receiving IV thrombolysis. DISCUSSION:The results from this trial will determine whether an enhanced care pathway delivered by paramedics can increase thrombolysis delivery rates. TRIAL REGISTRATION:ISRCTN registry, ISRCTN12418919 . Registered on 5 November 2015.

Project description:IntroductionCurrent antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate.Methods and analysisIn this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission.Ethics and disseminationThis trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD.Trial registration numberClinicalTrials.gov: NCT04682899.

Project description:BackgroundPneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment.AimsThis trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke.MethodsIn this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549).ResultsIn the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45-1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001).ConclusionPCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.

Project description:BACKGROUND:Acute pancreatitis (AP) is associated with high morbidity and mortality in its most severe forms. Most patients with severe AP require intubation and invasive mechanical ventilation, frequently for more than 7 days, which is associated with the worst outcome. Recent increasing evidence from preclinical and clinical studies support the beneficial effects of epidural analgesia (EA) in AP, such as increased gut barrier function and splanchnic, pancreatic and renal perfusion, decreased liver damage and inflammatory response, and reduced mortality. Because recent studies suggest that EA might be a safe procedure in the critically ill, we sought to determine whether EA reduced AP-associated respiratory failure and other major clinical outcomes in patients with AP. METHODS AND ANALYSIS:The Epidural Analgesia for Pancreatitis (EPIPAN) trial is an investigator-initiated, prospective, multicentre, randomised controlled two-arm trial with assessor-blinded outcome assessment. The EPIPAN trial will randomise 148 patients with AP requiring admission to an intensive care unit (ICU) to receive EA (with patient-controlled epidural administration of ropivacaine and sufentanil) combined with standard care based on current recommendations on the treatment of AP (interventional group), or standard care alone (reference group). The primary outcome is the number of ventilator-free days at day 30. Secondary outcomes include main complications of AP (eg, organ failure and mortality, among others), levels of biological markers of systemic inflammation, epithelial lung injury, renal failure, and healthcare-associated costs. ETHICS AND DISSEMINATION:The study was approved by the appropriate ethics committee (CPP Sud-Est VI). Informed consent is required. If the combined application of EA and standard care proves superior to standard care alone in patients with AP in the ICU, the use of EA may become standard practice in experienced centres, thereby decreasing potential complications related to AP and its burden in critically ill patients. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:NCT02126332.

Dataset Information

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial.

Background

Methods

Discussion

Trial registration

Publications

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial.

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