Efficacy of Prophylactic Treatment With Antibiotics During Concomitant Chemoradiotherapy in Patients With Head and Neck Cancer to Prevent Aspiration Pneumonia (PANTAP)
Patients with locally advanced head and neck cancer treated with chemo-radiotherapy have (during and shortly after this treatment) a high risk of developing pneumonia by aspiration. This pneumonia is often associated with a hospital admission and affects the quality of life.
The purpose of the study, is to determine whether prophylactic antibiotics may decrease the development of pneumonia. Prophylactic antibiotics means that there are no signs of pneumonia are already
Head and Neck Cancer
Drug: amoxicillin/clavulanic acid suspension
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Efficacy and Cost Efficacy of Prophylactic Treatment With Antibiotics During Concomitant Chemoradiotherapy in Patients With Locally Advanced Head and Neck Cancer to Prevent Aspiration Pneumonia. A Randomized Phase II-III Study|
- the number of definite pneumonia and/ or suspected pneumonia [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
Evidence of pneumonia on chest radiography or 3 or more of the following:
Sustained fever (temperature> 100 f [38°C]), Rales or rhonchi on chest auscultation Sputum Gram stain showing substantial leukocytes Sputum culture showing a respiratory pathogen
At least 2 of the 4 following features are present, without evidence of pneumonia on chest radiography:
Sustained fever (temperature> 100 f [38°C]) Rales or rhonchi on chest auscultation Sputum Gram stain showing substantial leukocytes Sputum culture showing a respiratory pathogen
- effects on Quality of Life [ Time Frame: Baseline, Day 28 last day of CRT, 3,5 months after CRT ] [ Designated as safety issue: No ]
to investigate the effects on QoL after prophylactic treatment with antibiotics
Patients fill in the following questionnaires:
QLQ-C30, EORTC H&N35, PSHHN, EQ-5D and the VAS, SF-36
- Number and kind of positive blood cultures [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
- number of admissions to hospital [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
- Number of days of admission [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]
- Effects on mortality [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]Mortality due to definite and/or suspected pneumonia
- effects on mucositis: grade and duration [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]Mucositis grade according to CTCAE v.4.0 and duration
- side effects of amoxicillin/clavulanic acid [ Time Frame: from day 1 of 1 CRT until 3,5 mnd after the last CRT ] [ Designated as safety issue: No ]side effects of amoxicillin/clavulanic acid
- Effects on numbers and causative agents of infections at other sites [ Time Frame: during follow up ] [ Designated as safety issue: No ]numbers and causative agents of infections at other sites during follow up (3.5 months after the end of CRT)
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
No Intervention: No prophylactic treatment
When a lower airway infection is suspected cultures will be taken and a chest radiography will be made; after that the standard care will be given (in most patients admission to hospital and start of intravenous antibiotics).
Experimental: prophylactic treatment
Administration of prophylactic amoxicillin/clavulanic acid suspension, 625 mg tid, start day 29 after the start of CRT until 14 days after the end of CRT. If a lower airway infection is suspected cultures will be taken and a chest radiography will be made; after that the standard care will be given (in most patients admission to hospital and start of intravenous antibiotics)
Drug: amoxicillin/clavulanic acid suspension
625 mg tid, start day 29 after the start of CRT until 14 days after the end of CRT
Other Name: The total duration of the use of amoxicillin /clavulanic acid suspension will be between 20 and 27 days.
Concomitant chemoradiotherapy (CRT) is used in locally advanced head and neck cancer (LAHNC). It will be administered to patients for unresectable disease or for organ preservation as primary treatment. Furthermore, it can be used as postoperative treatment in case high risk recurrent disease is present. This treatment induces a high rate of acute toxicity, such as mucositis, dermatitis, dysphagia, anorexia, and pain. Swallowing dysfunction and aspiration are seen in a high proportion (30%-100%) of patients and with an immense impact on Quality of life (QoL).
Around half of the patients will develop an aspiration pneumonia during or shortly after the treatment.
Patients, who develop fever during concomitant chemoradiotherapy, are most of the time admitted in the hospital. In the differential diagnosis pneumonia is on the first place in all those patients. The standard diagnostic procedures consist of a chest X-ray and culture of the sputum and blood. Pneumonia can lead to mortality in this frail patient group.
The treatment of patients treated with chemoradiotherapy who develop fever and have a definite or suspected pneumonia, is administration of antibiotics, most frequently intravenous amoxicillin/clavulanic acid.
LAHNC patients who are smoking and/or with malnutrition are at the highest risk of getting a pneumonia during or after radiotherapy. Because smoking is one of the risk factors of developing head and neck cancer chronic obstructive pulmonary disease (COPD) is frequently present in this group. Also, COPD is a known risk factor for developing pneumonias.
Aspiration is seen in all primary sites of head and neck cancer, sometimes it is seen more frequently in patients with cancer of the larynx and hypopharynx. No data of prophylactic administration of antibiotics are available in LAHNC patients. However, a Cochrane review was published to assess the effects of prophylactic antibiotic regimens for the prevention of respiratory tract infections(RTIs) and overall mortality in adults receiving intensive care.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01598402
|Contact: C. van Herpen, Md||+31 24 361 03 firstname.lastname@example.org|
|Contact: C. Driessen, drs||+31 24 361 11 11 ext *pager: email@example.com|
|Arnhem, Gelderland, Netherlands, 6800 TA|
|Contact: J. Blaisse, Md +31 26-3788888 firstname.lastname@example.org|
|Contact: S. Brouwer +31 26-3788888 email@example.com|
|Principal Investigator: J. Blaisse, Md|
|University Medical Center Nijmegen st Radboud||Recruiting|
|Nijmegen, Gelderland, Netherlands, 6525 GH|
|Contact: C. van Herpen, Md +31 24 361 03 53 firstname.lastname@example.org|
|Contact: C. Driessen, drs +31 24 361 11 11 ext pager 3438 email@example.com|
|Principal Investigator: C.M.L van Herpen, Md, Phd|
|Sub-Investigator: C. Driessen, drs|
|Medisch Centrum Alkmaar||Not yet recruiting|
|Alkmaar, Netherlands, 1815 JD|
|Contact: C. Smorenburg, Md +31 72-5484444 firstname.lastname@example.org|
|Contact: M. Komen +31 72-5484444 email@example.com|
|Principal Investigator: C. Smorenburg, Md|
|University Medical Centre Groningen||Recruiting|
|Groningen, Netherlands, 9700 RB|
|Contact: J. Gietema, Md +31 50 361 61 61 firstname.lastname@example.org|
|Contact: G. Sieling +31 50 361 61 61 email@example.com|
|Principal Investigator: J. Gietema, Md|
|Medisch centrum Leeuwarden||Not yet recruiting|
|Leeuwarden, Netherlands, 8934 AD|
|Contact: E. Fiets, Md +31 58-2866666 firstname.lastname@example.org|
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|Principal Investigator: E. Fiets, Md|
|Academical Hospital Maastricht (AZM)||Not yet recruiting|
|Principal Investigator: A. Hoeben, PhD|
|Principal Investigator:||C. van Herpen, MD||University Medical Centre Nijmegen|