Procalcitonin in Early Antibiotic Interruption in Patient With Bacterial Pulmonary infeCtion and Acute Heart Failure (EPICAD)

• ClinicalTrials.gov Identifier: NCT02787603
• Recruitment Status: Completed
• First Posted: June 1, 2016
• Last Update Posted: June 6, 2017
• Sponsor: University of Sao Paulo General Hospital
• Collaborator: BioMérieux
• Information provided by (Responsible Party): University of Sao Paulo General Hospital

Tracking Information

• First Submitted Date: May 25, 2016
• First Posted Date: June 1, 2016
• Last Update Posted Date: June 6, 2017
• Actual Study Start Date: January 2015
• Actual Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 25, 2016): Total period of antibiotic therapy [ Time Frame: 30 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 25, 2016)

• hospitalization [ Time Frame: 30 days ]
• mortality [ Time Frame: 30 days ]
• PCT levels during antibiotic therapy [ Time Frame: 5 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Procalcitonin in Early Antibiotic Interruption in Patient With Bacterial Pulmonary infeCtion and Acute Heart Failure
• Official Title: Evaluation of Procalcitonin in the Early Antibiotic Therapy Interruption in Patient With Bacterial Pulmonary infeCtion and Decompensated Acute Heart Failure
• Brief Summary: Introduction: Acute Heart Failure is frequently decompensated by pulmonary infection, but the diagnosis of pulmonary infection sometimes is difficult in these patients due to similar signals and clinical symptoms in both pathologies. Furthermore, when it is possible the diagnosis of pulmonary infection, physicians may have difficult to determine etiology and delaying antibiotic therapy. Procalcitonin (PCT) have been used like a biomarker to determine the period of use of antibiotics in patients with acute respiratory infections. It is specific for bacterial infections and it have showed as a marker of severity infection and may help to determine interruption period of antibiotic therapy in a safety way for the patient. Aim: Evaluate levels of PCT related to interruption of antibiotics in patients with decompensated acute heart failure (DAHF) with suspected bacterial pulmonary infection. Methods: In this pilot project will be included around 100 patients, randomized in two groups: group A (PCT levels may guide the interruption of antibiotic at day 5) or group B (antibiotic period will be determined by the physician without the knowledge of PCT levels). Will be collected laboratorial and clinical data at days 0,3 and 5. Both groups will be compared to evaluate PCT levels and total period of antibiotic therapy, hospitalization and readmission in 30 days. This study will determine the sensibility/specificity of PCT in patients with DAHF.
• Detailed Description: It is a single-center study, randomized, controlled, prospective cohort and interventional not blind. DAHF diagnosis will consider symptoms, physical examination, x ray and other image methods and BNP ou NTproBNP levels. Pulmonary infection diagnosis will "Infectious Disease Society of America / American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults" criteria, that include fever, cough, sputum, pleuritic pain, positive pulmonary image and physical examination. PCT and NTproBNP levels will be measured in miniVIDAS® (bioMérieux Clinical Diagnostics, France). Statistics includes descriptive analysis. Parametric data will be evaluated using T test and non parametric data with Mann-Whitney-Wilcoxon test. Multivariative analysis related to diagnosis, mortality and morbidity will be performed by Cox regression model. Sensibility and specificity will be calculated by ROC curve. Statistical significancy will be considered when p<0.05.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Respiratory Tract Infections
• Pneumonia, Bacterial
• Heart Failure

Intervention

Other: Interruption of antibiotic treatment due to PCT measurement

In group A at day 5, if the patient shows no clinical signs of infection and PCT levels < 0,25ng/mL OR PCT > 0,25 ng/mL AND 80% reduction in comparison with day 0 PCT levels, antibiotic will be interrupted. If there is a constant level or decrease less than 80% when compared day 0 or 5, there is no change in antibiotic treatment.

Study Arms

• Experimental: group A
  Interruption of antibiotic treatment due to PCT measurement
  Intervention: Other: Interruption of antibiotic treatment due to PCT measurement
• No Intervention: group B
  Antibiotic therapy period will be determined by the physician without the knowledge of PCT levels.

Publications *

• Maisel A, Neath SX, Landsberg J, Mueller C, Nowak RM, Peacock WF, Ponikowski P, Möckel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng LL, Daniels LB, Christenson RH, Potocki M, McCord J, Terracciano G, Hartmann O, Bergmann A, Morgenthaler NG, Anker SD. Use of procalcitonin for the diagnosis of pneumonia in patients presenting with a chief complaint of dyspnoea: results from the BACH (Biomarkers in Acute Heart Failure) trial. Eur J Heart Fail. 2012 Mar;14(3):278-86. doi: 10.1093/eurjhf/hfr177. Epub 2012 Feb 2.
• Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 2011 Sep 22;9:107. doi: 10.1186/1741-7015-9-107. Review.
• Bafadhel M, Clark TW, Reid C, Medina MJ, Batham S, Barer MR, Nicholson KG, Brightling CE. Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. 2011 Jun;139(6):1410-1418. doi: 10.1378/chest.10-1747. Epub 2010 Oct 28.
• Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Régnier B, Brun-Buisson C, Chastre J, Wolff M; PRORATA trial group. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010 Feb 6;375(9713):463-74. doi: 10.1016/S0140-6736(09)61879-1. Epub 2010 Jan 25.
• Schuetz P, Kutz A, Grolimund E, Haubitz S, Demann D, Vögeli A, Hitz F, Christ-Crain M, Thomann R, Falconnier C, Hoess C, Henzen C, Marlowe RJ, Zimmerli W, Mueller B; ProHOSP Study Group. Excluding infection through procalcitonin testing improves outcomes of congestive heart failure patients presenting with acute respiratory symptoms: results from the randomized ProHOSP trial. Int J Cardiol. 2014 Aug 20;175(3):464-72. doi: 10.1016/j.ijcard.2014.06.022. Epub 2014 Jun 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 5, 2017): 46
• Original Estimated Enrollment (submitted: May 25, 2016): 100
• Actual Study Completion Date: April 2017
• Actual Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• DAHF diagnosis and suspected pulmonary infection
• BNP ≥ 500 pg/mL or NTproBNP ≥ 450 pg/mL for patients until 50 years old.
• BNP ≥ 500 pg/mL or NTproBNP ≥ 900 pg/mL for patients with 51 - 75 years old.
• BNP ≥ 500 pg/mL or NTproBNP ≥ 1800 pg/mL for patients older than 75 years.

Exclusion Criteria:

• Antibiotic use (oral or endovenous) in the last 15 days;
• Acute coronary syndrome;
• Creatinine > 3,0 mg/dL or hemodialysis;
• Pregnancy;
• Second suspectec infection;
• Suspected pulmonary thromboembolism;
• cancer;
• myocarditis.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT02787603
• Other Study ID Numbers: PSInCor-Procalcitonin Clinical
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: University of Sao Paulo General Hospital
• Study Sponsor: University of Sao Paulo General Hospital
• Collaborators: BioMérieux

Investigators

• Principal Investigator: Mucio Tavares, PhD MD; Unidade Clínica de Emergência

• PRS Account: University of Sao Paulo General Hospital
• Verification Date: January 2017