A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis (CISTIC)

The Alfred

Status and phase: Unknown; Phase 4

Conditions: Cystic Fibrosis

Treatments: Drug: Intermittent, short infusion Ticarcillin-clavulanate; Drug: Intermittent, short infusion Ceftazidime; Drug: Continuous infusion Ticarcillin-clavulanate; Drug: Continuous infusion Cefepime; Drug: Intermittent, short infusion Piperacillin tazobactam; Drug: Intermittent, short infusion Meropenem; Drug: Continuous infusion Piperacillin tazobactam; Drug: Continuous infusion Ceftazidime; Drug: Intermittent, short infusion Cefepime; Drug: Continuous infusion Meropenem

Study type: Interventional

Funder types: Other

Identifiers

NCT01667094

U1111-1132-8291 (Other Identifier)

249/12

Details and patient eligibility

About

Cystic fibrosis (CF) is an inherited disorder which results in increased thickness of secretions, especially in the lungs. By adulthood, the majority of patients with CF will have a bacteria living in their lungs, called Pseudomonas aeruginosa which can cause lung infections. This usually results in worsening respiratory symptoms and often an acute deterioration in their lung function. They are usually treated with antibiotics that target the Pseudomonas aeruginosa. These antibiotics are typically given as short intravenous infusions several times a day. This study aims to compare the standard method of giving these antibiotics with a different strategy of giving these antibiotics to see if this can improve the outcomes of treatment of these infections and reduce the amount of Pseudomonas aeruginosa in the lungs of these patients. This strategy consists of giving the same antibiotics continuously, to ensure there is always enough antibiotic in the bloodstream and the lung to be able to kill the bacteria.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients >= 18 years of age,

2. Pseudomonas aeruginosa isolated in sputum within the last 12 months,

3. has an acute infective exacerbation, defined by international standards of 2 or more of the following in the last 2 weeks:

   • change sputum volume or colour,
   • increased cough,
   • increased dyspnoea,
   • increased malaise, fatigue or lethargy,
   • anorexia or weight loss,
   • decrease in pulmonary function by 10% or more, or
   • new radiographic changes

Exclusion criteria

1. patients < 18 yrs of age,
2. patients that do not meet the criteria for an acute infective exacerbation,
3. concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory failure,
4. impaired renal function with an estimated creatinine clearance < 60 mls/min,
5. patients allergic to ß-lactam antibiotics,
6. aminoglycoside contra-indicated,
7. intravenous antibiotics in the last 2 weeks, prior to this admission,
8. received more than 24 hours of intravenous antibiotics in this admission,
9. previous lung transplantation,
10. pregnancy or lactation, or
11. inability to consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

50 participants in 2 patient groups

Intermittent, short infusion

Active Comparator group

Description:

Infusion over 30 minutes of either: Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24 Antibiotic chosen by treating physician

Treatment:

Drug: Intermittent, short infusion Ticarcillin-clavulanate

Drug: Intermittent, short infusion Piperacillin tazobactam

Drug: Intermittent, short infusion Meropenem

Drug: Intermittent, short infusion Ceftazidime

Drug: Intermittent, short infusion Cefepime

Continuous infusion

Experimental group

Description:

Continuous infusion of either: Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g Antibiotic chosen by treating physician

Treatment:

Drug: Continuous infusion Piperacillin tazobactam

Drug: Continuous infusion Meropenem

Drug: Continuous infusion Ceftazidime

Drug: Continuous infusion Ticarcillin-clavulanate

Drug: Continuous infusion Cefepime