Reduction of Antibiotic Therapy by Biomakers in Patients With CAP Episodes (REDUCE Study) (REDUCE)

The purpose of this study is to evaluate two different treatment strategies in patients admitted to hospital with Community Acquired Pneumonia. The investigators hypothesize treatment according to both procalcitonin (PCT) and C-reactive protein (CRP) will be effective in reducing the length of antibiotic treatment.

Study Overview

• Status: Completed
• Conditions: Community Acquired Pneumonia
• Intervention / Treatment: Drug: Treatment according to current guidelines; Drug: Discontinuation of treatment according to CRP levels; Drug: Discontinuation of treatment according to PCT levels

• Study Type: Interventional
• Enrollment (Actual): 468
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord Holland
    • Alkmaar, Noord Holland, Netherlands, 1815JD
      • Medical Centre Alkmaar
    • Amsterdam, Noord Holland, Netherlands, 1006BK
      • Slotervaart Hospital
  • Overijssel
    • Zwolle, Overijssel, Netherlands, 8025 AB
      • Isala Clinics

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:

Male and female patients with a diagnosis of CAP and all criteria listed below:

1. Age 18 or above, no upper age limit will be employed.
2. Patients must require hospitalisation.

3. Clinical presentation of an acute illness with one or more of the following symptoms:

   1. Temperature ≥ 38.0 ⁰C (100.4°F)
   2. Dyspnoea
   3. Cough (with or without expectoration of sputum)
   4. Chest pain
   5. Malaise or fatigue
   6. Myalgia
   7. Gastro-intestinal symptoms
   8. Rales, rhonchi or wheezing
   9. Egophony or bronchial breath sounds
4. New consolidation(s) on the chest radiograph.
5. Written informed consent obtained.
6. (Pre-event) Life expectancy > 30 days

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

1. (Severe) immunosuppression (e.g. HIV infection, chemotherapy, use of immunosuppressants).
2. Active neoplastic disease.
3. Obstruction pneumonia (e.g. from lung cancer).
4. Aspiration pneumonia.
5. Pneumonia that developed within 8 days after hospital discharge.
6. Unable and/or unlikely to comprehend and/or follow the protocol.
7. Pregnant and/or lactating women.
8. Other infection that requires treatment with antibiotics

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Common clinical practice; Treatment according to current guidelines. Often a 7 day course of antibiotics. Initial treatment should be broad spectrum antibiotics and can be narrowed down if a specific pathogen is identified.	Drug: Treatment according to current guidelines; Often a 7 days course of antibiotics, treatment may be extended if the attending physician deems it necessary.; Other Names: Broad spectrum antibiotics; Small spectrum antibiotics
EXPERIMENTAL: CRP-guided treatment; Treatment according to CRP levels. Patients will be started on broad spectrum antibiotics for at least 3 days, treatment can be switched to small-spectrum antibiotics if a specific pathogen is identified. From day 4 to 7 daily blood tests will be performed in order to evaluate whether or not treatment can be discontinued. If treatment is discontinued, no more blood tests will be performed.	Drug: Discontinuation of treatment according to CRP levels; The cutoff point is a CRP below 100 mg/L and a reduction to 50% of the initial value.; Other Names: Broad spectrum antibiotics; Small spectrum antibiotics
EXPERIMENTAL: PCT guided treatment; Treatment according to PCT levels. Patients will be started on broad spectrum antibiotics for at least 3 days, treatment can be switched to small-spectrum antibiotics if a specific pathogen is identified. From day 4 to 7 daily blood tests will be performed in order to evaluate whether or not treatment can be discontinued. If treatment is discontinued, no more blood tests will be performed.	Drug: Discontinuation of treatment according to PCT levels; The cutoff point is a PCT below 0.25 mcg/L or a reduction to 10% of the initial value.; Other Names: Broad spectrum antibiotics; Small spectrum antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Length of antibiotic treatment	End of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay		End of the study
Clinical response	Cure - resolution or improvement of symptoms and clinical signs related to pneumonia without the need for additional or alternative antibiotic therapy Failure - persistence or progression of all signs and symptoms of the acute process after randomisation or the development of a new pulmonary or extrapulmonary respiratory tract infection, or the progression of abnormalities on chest radiograph after randomisation, or death due to pneumonia, or the inability to complete the study owing to adverse events Indeterminate - patient receives less than 80% of the study drug for reasons other than clinical failure, a concomitant infection outside the respiratory tract requiring antibiotic treatment, lost to follow-up, or death unrelated to the primary diagnosis.	End of the study
30-day mortality	All cause	End of the study, periodically by the DSMB
Time to clinical stability	Patients are considered clinically stable if they fulfill all of these criteria: Temperature equal to or below 37.8 degrees celsius, heart rate equal to or below 100 beats per minute, respiratory rate equal to or below 24 breaths per minute, systolic blood pressure equal to or above 90 mmHg, arterial oxygen saturation equal to or above 90 percent or pO2 equal to or above 60 mmHg on room air, ability to maintain oral intake, normal mental status.	End of the study
Relapse rate		End of the study

Collaborators and Investigators

• Sponsor: Medical Center Alkmaar
• Collaborators: Foreest Medical School; Pulmoscience
• Investigators: Study Director: Ruud Duijkers, MSc, MD, Medisch Centrum Alkmaar; Principal Investigator: Wim G Boersma, MD, PhD, MSc, Medisch Centrum Alkmaar; Study Chair: Dominic Snijders, MSc, PhD, MD, Slotervaart Ziekenhuis

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 5, 2013
• Primary Completion (ACTUAL): January 20, 2017
• Study Completion (ACTUAL): January 20, 2017

Study Registration Dates

• First Submitted: September 30, 2013
• First Submitted That Met QC Criteria: October 14, 2013
• First Posted (ESTIMATE): October 17, 2013

Study Record Updates

• Last Update Posted (ACTUAL): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 1-Duijkers