The efficacy and safety of co-trimoxazole therapy in patients with idiopathic interstitial pneumonia - TIPAC

Conditions: Idiopathic Interstitial Pneumonia
MedDRA version: 9.1Level: LLTClassification code 10022619Term: Interstitial pulmonary fibrosis

Registration Number: EUCTR2007-002324-15-GB

Lead Sponsor: niversity of East Anglia

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

1.Male or female, aged greater than 40 years
2.Female subjects must be of non-childbearing potential, defined as follows
•postmenopausal females who have had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml
•females who have had a hysterectomy or bilateral oophorectomy for at least 6 weeks
3.Able to provide informed consent
4.A clinical labelled diagnosis of fibrotic idiopathic interstitial pneumonia with HRCT scan features compatible with Usual Interstitial Pneumonia (UIP) or Fibrotic Non-specific Interstitial Pneumonia (NSIP). The following criteria adapted from the ATS/ERS consensus statement will be used for the diagnosis the clinical manifestation of UIP (idiopathic pulmonary fibrosis):
•Major Criteria (All present)
oExclusion of other known causes of interstitial lung disease, such as drug toxicities, environmental exposures, and collagen vascular diseases
oAbnormal pulmonary function studies that include evidence of restriction with or without impaired gas exchange
oBibasal reticular abnormalities with minimal ground glass opacities on HRCT
•Minor criteria (two out of three features)
oInsidious onset of otherwise unexplained dyspnoea on exertion
oDuration of illness 3 months
oBibasal inspiratory crackles (dry or ‘‘Velcro-’’ type in quality)
Patients with clinical diagnosis of non-specific interstitial pneumonia will be entered if fibrotic features are predominant on HRCT. Histology will not be required as an entry criterion.
5.Patients will have had initial treatment of prednisolone +/- azathioprine, as indicated and described in the current BTS guidelines, without a without a significant response to immunosuppressive therapy that would make the physician doubt the diagnosis of fibrotic idiopathic interstitial pneumonia.
6.Patients should be on stable treatment regimen for at least 6 weeks. This will include oral prednisolone up to a dose of 20mg per day +/- azathioprine. Patients receiving higher doses of up to 0.5mg/kg may be enrolled in exceptional circumstances after discussion with the principal investigator.
7.MRC dyspnoea score of ?2
8.A normal serum folate and B12 (to ensure no bone marrow or neurological adverse effects occur with folate therapy to B12 deficient individuals) is required at screening.
9.Subjects have a 12 lead ECG recording that does not demonstrate any clinically important abnormality that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.A secondary cause for pulmonary fibrosis including a diagnosis of asbestosis, drug induced pulmonary fibrosis, collagen vascular disease or other secondary pulmonary fibrosis.
2.A recognised significant co-existing respiratory disorder.
3.Long-term oxygen therapy.
4.Receiving anti-oxidant therapy including acetylcysteine within the last 6 weeks.
5.A respiratory tract infection within the last 2 months
6.Overt and persistent heart failure, a myocardial infarction within 3 years, ischaemic heart disease requiring more than one regular therapy or a clinically significant uncontrolled arrhythmia (including Mobitz type II or third degree heart block).
7.Significant medical, surgical or psychiatric disease that in the opinion of the patients’ attending physician would affect subject safety or influence the study outcome.
8.Women who are pregnant or are breast-feeding.
9.Patients receiving immunosuppressant medication (with the exception of prednisolone and azathioprine according to guidelines).
10.Co-trimoxazole allergy or intolerance and patients receiving medication known to interact with co-trimoxazole.
11.Untreated folate or B12 deficiency.
12.Known glucose-6-phosphate dehydrogenase deficiency.
13.Receipt of an investigational drug or biological agent within the 4 weeks prior to entry in to this study.
14.Patients with evidence of drug or alcohol misuse

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy and safety of 6 months therapy with co-trimoxazole 960mg twice daily when added to standard treatment/care in a placebo controlled study of patients with idiopathic interstitial pneumonia;Secondary Objective: The secondary objective is to estimate the incremental cost effectiveness of co-trimoxazole plus standard care compared with standard care alone;Primary end point(s): Change in forced vital capacity<br>Change in 6 minute walking distance and desaturation<br>Change in MRC breathlessness score<br>Change in total lung capacity<br>Change in total lung diffusing capacity of carbon monoxide<br>Change in St Georges Respiratory Questionnaire

Secondary Outcome Measures