Assessing Effectiveness of Community Acquired Pneumonia Treatment by Continuous Pneumonia Severity Score

Assessing Effectiveness of Community Acquired Pneumonia Treatment by Continuous Pneumonia Severity Score: a Prospective Observational Study and Randomized Controlled Trial

Community acquired pneumonia (CAP) is a common respiratory infection and is the main cause of ICU admission and death in adults. Because of most patients were treated empirically against suspected causative microorganism, it is important to assess the effectiveness of treatment after 3 days of anti-infective therapy. However, the criteria for treatment failure is lack of a clear-cut and validated definition from the CAP guidelines.

Pneumonia severity scores is a wide-used severity rating system for treatment selection and outcome prediction for CAP. So far, the pneumonia severity scores only used once before the treatment started. Considering the pneumonia severity scores could reflect the severity of pneumonia, it is reasonable to assume that the change of pneumonia severity scores could reflect the patients' condition and the effectiveness of the treatment. This trail will be designed to validate the feasibility of assessing effectiveness of CAP treatment by using continuous pneumonia severity score.

Study Overview

• Status: Unknown
• Conditions: Community-acquired Pneumonia
• Intervention / Treatment: Procedure: changes of Pneumonia Severity Score

Detailed Description

The applicant has established a CAP patients database and found a new effective pneumonia severity score: Expand-CURB. According to the retrospective study results, applicant found the changes of pneumonia severity score could reflect the patients'condition and was the independent risk factor for 30-day mortality. More specifically, if the patients'Expand-CURB score was not improved after 3-5 days of initial treatment, the odds ratio of 30-day mortality was 5.571 and 5.249 (95%CI 1.831-15.051, P=0.002) by univariate analysis and multivariate analysis (the multivariate was adjusted by the initial severity of pneumonia).

In addition, the applicant found the changes of serum CRP(C reactive protein ) before and after initial treatment also associated the patients'outcomes. If the serum CRP decreased less than 40% or not lower than 20mg/dl after the initial treatment, the odds ratio of 30-day mortality will be 3.692 and 3.806 (95%CI 1.867-7.756, P<0.001) by univariate analysis and multivariate analysis.

In conclusion, the applicant established three criteria for assessing effectiveness of CAP treatment:

1. Effective treatment by PSI: the PSI score decreased after 3-5 days the initial treatment.
2. Effective treatment by Expand-CURB: the Expand-CURB score decreased after 3-5 days the initial treatment.
3. Effective treatment by serum CRP: the serum CRP decreased more than 40% or lower than 20mg/dl after 3-5 days the initial treatment.

Furthermore, the applicant found combined pneumonia severity scores with CRP could predict the 30-day mortality more efficiently. The OR for both CRP and PSI treatment failure was 2.377 (95%CI 1.100-5.136, P=0.028). And the OR for both CRP and Expand-CURB treatment failure was 7.332 (95%CI 1.563-34.385, P=0.012). Therefore, it is reasonable to assume that the change of pneumonia severity scores and CRP could reflect the patients'condition and the effectiveness of the treatment.

To validate the feasibility of assessing effectiveness of CAP treatment by using continuous pneumonia severity score and changes of CRP, applicant intend to randomly allocate the patients into three arms: Comprehensive evaluation group, PSI evaluation group and Expand-CURB evaluation group. Patients who did not agree to participate the randomized controlled study will be asked whether they agree to provide their clinical data for prospective observational studies.

The primary outcomes will be 30-day mortality and ICU admission. The second outcome is length of hospital stay.

• Study Type: Interventional
• Enrollment (Anticipated): 2000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jinliang Liu, MD; Phone Number: +86 13867496840; Email: 2511063@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • SAHZhejiangU
      • Contact: Jinliang Liu, MD; Phone Number: +86 13867496840; Email: 2511063@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• community acquired pneumonia(by CTS or IDSA/ATS guidelines)
• severe community acquired pneumonia(PSI scores >= 90 or Expand-CURB scores >= 4);

Exclusion Criteria:

• HIV patients
• Other immunodeficiency disorders (neutropenia, hematologic and solid tumors undergoing chemoradiotherapy, organ transplantation, and long-term treatment with glucocorticoid and cytokine antagonists).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Comprehensive evaluation group; The effectiveness of initial treatment and the next treatment plan were determined based on the CAP guidelines of Chinese Thoracic Society (CTS) or Infectious Diseases Society of America/American Thoracic Society(IDSA/ATS). The evaluation process was independently evaluated and documented by at least two clinicians. In case of disagreement, the final determination shall vote on the majority of votes.	Procedure: changes of Pneumonia Severity Score; assessing effectiveness of CAP treatment by using continuous pneumonia severity score
EXPERIMENTAL: PSI evaluation group; The changes of PSI scores and serum CRP were used to evaluate the therapeutic effects. If both PSI scores and CRP suggest that treatment is effective, the initial treatment will be maintained. If either of PSI scores or serum CRP suggest that treatment is effective, the initial treatment can be maintained, but need to be reviewed in the next 3-5 days. If both PSI scores and serum CRP suggest that the treatment is failed, the initial treatment should be changed. The change of initial treatment is not limited to antibiotics, but also include using glucocorticoid, ICU admission, mechanical ventilation according to the patients' condition.	Procedure: changes of Pneumonia Severity Score; assessing effectiveness of CAP treatment by using continuous pneumonia severity score
EXPERIMENTAL: Expand-CURB evaluation group; The changes of Expand-CURB scores and serum CRP were used to evaluate the therapeutic effects. If both Expand-CURB scores and CRP suggest that treatment is effective, the initial treatment will be maintained. If either of Expand-CURB scores or serum CRP suggest that treatment is effective, the initial treatment can be maintained, but need to be reviewed in the next 3-5 days. If both Expand-CURB scores and serum CRP suggest that the treatment is failed, the initial treatment should be changed. The change of initial treatment is not limited to antibiotics, but also include using glucocorticoid, ICU admission, mechanical ventilation according to the patients' condition.	Procedure: changes of Pneumonia Severity Score; assessing effectiveness of CAP treatment by using continuous pneumonia severity score
NO_INTERVENTION: Prospective observational group; Patients' Expand-CURB scores, PSI scores and serum CRP before and after 3-5 days of initial treatment will be recorded. And the initial treatment, whether the initial treatment was changed 3-5 days of initial treatment and the final outcomes (ICU admission, 30-day mortality, average length of stay) will be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients for ICU admission	Rate of patients who received ICU treatment during hospitalization. The numerator is the number of patients who received ICU treatment during hospitalization. The denominator is the number of all the enrolled patients.	through study completion, an average of 10 days
Rate of all-caused mortality within 30 days.	Rate of all-caused death occurring within 30 days during hospitalization. The numerator is the number of patients who defined as death occurring within 30 days of hospitalization. The denominator is the number of enrolled patients.	through study completion, an average of 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay for patients	The duration of a single episode of hospitalization. Inpatient days are calculated by subtracting day of admission from day of discharge.	through study completion, an average of 10 days

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

General Publications

• Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2(Suppl 2):S27-72. doi: 10.1086/511159. No abstract available.
• Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997 Jan 23;336(4):243-50. doi: 10.1056/NEJM199701233360402.
• Liu JL, Xu F, Zhou H, Wu XJ, Shi LX, Lu RQ, Farcomeni A, Venditti M, Zhao YL, Luo SY, Dong XJ, Falcone M. Expanded CURB-65: a new score system predicts severity of community-acquired pneumonia with superior efficiency. Sci Rep. 2016 Mar 18;6:22911. doi: 10.1038/srep22911. Erratum In: Sci Rep. 2018 Aug 09;8:47005.
• Welte T, Kohnlein T. Global and local epidemiology of community-acquired pneumonia: the experience of the CAPNETZ Network. Semin Respir Crit Care Med. 2009 Apr;30(2):127-35. doi: 10.1055/s-0029-1202941. Epub 2009 Mar 18.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2020
• Primary Completion (ANTICIPATED): June 30, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: October 17, 2019
• First Submitted That Met QC Criteria: October 20, 2019
• First Posted (ACTUAL): October 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 20, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Community-acquired Pneumonia; Pneumonia severity scores
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: I2019001440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No