The Effectiveness and Risks of Treating People With Idiopathic Pulmonary Fibrosis With the Addition of Lansoprazole: a Randomised Placebo-controlled Multi-centre Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 298
- 试验地点
- 57
- 主要终点
- Absolute change in percent predicted (%) forced vital capacity (FVC)
研究概览
简要总结
IPF is a progressive scarring lung condition causing coughing and breathlessness. IPF patients often have reflux disease meaning stomach acid may be breathed into the lungs, potentially damaging them. Medicines which stop stomach acid production, proton pump inhibitors (PPIs), can be used to reduce reflux symptoms including heartburn. Some researchers suggest PPIs also reduce IPF progression.
This research aims to see if IPF progresses slower if treated with PPIs. Based on the results, we will be able to recommend whether or not IPF patients should take PPIs.
This trial will involve 298 IPF patients from approximately 37 UK hospitals. At the beginning of the study, we will ask patients to start performing weekly breathing tests at home using equipment provided, and ask those with a cough to use a device to count the number of times they cough in 24hours. We will ask them to answer two questions rating their coughing and breathlessness, and complete questionnaires on their coughing, IPF, sleep habits and general condition. People will be given a PPI, called lansoprazole, or dummy tablets, twice per day for 12 months. They will be given a leaflet telling them what to do about reflux symptoms. At the end of the study, we will repeat these tests and analyse the results. We will record any side effects people may get. If people suffer side effects, they can reduce the dose.
People taking medicines that interact with PPIs or have other serious medical conditions won't be able to participate. People receiving PPIs will only be able to participate if they can stop taking their medication without their heartburn returning.
详细描述
Idiopathic pulmonary fibrosis (IPF) is a progressive and usually fatal lung disease with a poor prognosis. IPF patients frequently have other medical conditions as well, with reflux disease being one of the most common. Previous studies and a review of data already collected suggest that treatments used to reduce reflux disease symptoms, proton pump inhibitors (PPIs), may reduce IPF disease progression and improve survival rates. Current IPF treatment guidelines cautiously advise PPI treatment for IPF patients, however there hasn't been a study which investigates this specifically yet even though doctors and government groups have said one is needed. There are thought to be links between cough, reflux, sleep and IPF. As a result we will be asking a sub-group of patients to complete two 24 hour sessions of cough frequency monitoring as a sub-study. Some of these participants may be asked to wear a wrist-based activity and sleep monitor during these periods also. In addition, we will ask patients to complete two questionnaires on their sleeping habits to further investigate this link. At the end of the trial, we will able to recommend whether or not IPF patients should take PPIs routinely or not.
This project is a clinical trial of an investigational medicinal product (drug). The drug is well established and approved for use for another medical condition. The drug will be assessed against placebo (dummy) tablets, with patients allocated to either group by chance. Patients on the drug and dummy tablets will be assessed at the same time. Neither patients nor their doctors or the research team will know which treatment they have been allocated to. We will be running the study at approximately 37 hospitals across the UK.
All study visits may take place remotely without the participant needing to attend the hospital. However, face-to-face onsite visits are also permitted if preferred/feasible. All participants will receive central training via video call, with a trained clinical physiologist, following consent on how to complete domiciliary spirometry assessments. Further training will be provided during follow-up if deemed required following a review of the data. Questionnaires will be completed either electronically or by post.
Potentially eligible patients will be approached remotely or in clinic after being identified from local patient lists/databases. They will be given/sent the relevant study literature to consider participation in the study and will be followed-up by a member of the local research team after they have had at least 24hours to consider participating.
Interested patients will be invited to a virtual or face-to-face screening appointment where they will be counselled on the study and what it entails in order to provide informed consent to participate. The patient will then be asked to complete baseline questionnaires, provide demographic, medical history and concomitant medication, and any other relevant study information, complete spirometry assessments over 5 days at home using a domiciliary spirometer and provide a blood sample for safety in order for the investigator to confirm their eligibility for the trial. Patients may also provide a blood sample for analysis in future research if the visit takes place at the recruiting site. In addition, eligible participants may complete a 24hour period of cough frequency monitoring, and activity and sleep monitoring if applicable, if they have consented to do so. Patients in receipt of PPIs without a clear clinical indication for them at consent, will undergo a two week wash-out period (following agreement from the patient and their GP) to ascertain whether it is safe to stop this treatment and monitor whether their symptoms subside. Patients who remain asymptomatic at the end of this period will proceed to enter the study. For those whose symptoms return, PPI treatment will recommence and they will not enter the study. Once the results of all baseline assessments are known, patients will be randomised.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participant, care provider, investigator, outcomes assessor. Statistician. Double-blind
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged greater than or equal to 40 years.
- •A diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on local or regional multi-disciplinary consensus according to the latest international guidelines (50).
- •Patients may be receiving licensed anti-fibrotic medication (for at least 4 weeks prior to randomisation with no planned amendments for at least 4 weeks post-randomisation).
- •Able to provide informed consent.
- •Additional Inclusion Criteria for cough count sub-study:
- •1. Pre-existing diagnosis of persistent cough (defined as troublesome for more than 8 weeks prior to study enrolment).
排除标准
- •Patients unable to comply with study assessments including the ability to complete reliable spirometry assessments.
- •Concomitant use of a proton pump inhibitor (PPI) or prokinetic drugs (cisapride, domperidone, metoclopramide, erythromycin, prucalopride etc.) within 2 weeks prior to randomisation.
- •Patients with a self-reported respiratory tract infection within 4 weeks of screening (defined as two or more of: increased cough, sputum or breathlessness and requiring antimicrobial therapy).
- •Significant co-existing respiratory disease (defined as a respiratory condition that exhibits a clinically relevant effect on respiratory symptoms and disease progression as determined by the PI). The presence of traction bronchiectasis is permitted.
- •Patients with an FEV1/FVC<0.
- •Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety or influence the study outcomes including liver failure (e.g. serum transaminase > 2 x upper limit of normal (ULN), Bilirubin > 1.5 x ULN (unless the patient has Gilbert's Syndrome) and chronic kidney disease (CKD) greater than stage 3 , erosive oesophagitis, Barrett's oesophagus or any condition requiring lifelong proton pump inhibitor use.
- •Known allergy to proton pump inhibitors or the contents of placebo.
- •Concomitant use of atazanavir, ketoconazole, itraconazole, tacrolimus, methotrexate, fluvoxamine (see section 6.4.5).
- •Females who are of childbearing potential or lactating. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
- •Receipt of another investigational drug or biological agent associated with another clinical trial within the 4 weeks prior to TIPAL study enrolment or 5 times the drug half-life, whichever is the longer.
- •Receiving long-term oxygen therapy.
- •Patients with hypomagnesemia (defined as magnesium ≤0.6 mmol/L).
研究组 & 干预措施
Active treatment arm
Lansoprazole 30mg (as 2 x 15mg capsules) twice daily, 12 hours apart, for 12 months. IMP should be taken at least 30 minutes before food.
干预措施: Lansoprazole (Drug)
Matched-Placebo arm
Matched placebo 2 capsules twice daily, 12 hours apart, for 12 months. Treatment should be taken at least 30 minutes before food.
干预措施: Matched placebo (Other)
结局指标
主要结局
Absolute change in percent predicted (%) forced vital capacity (FVC)
时间窗: 12 months post-randomisation
Absolute change in percent predicted (%) forced vital capacity (FVC) at 12 months post-randomisation of lansoprazole versus placebo.
次要结局
- Cough frequency(3 months post-randomisation)
- Cough score(3, 6, 9 and 12 months post-randomisation)
- Cough related(3, 6, 9 and 12 months post-randomisation)
- Breathlessness(3, 6, 9 and 12 months post-randomisation)
- Disease specific quality of life(3, 6, 9 and 12 months post-randomisation)
- Health related quality of life(3, 6, 9 and 12 months post-randomisation)
- Total lung diffusing capacity of carbon monoxide(3, 6 and 12 months post-randomisation)
- Laboratory assessment(3, 6 and 12 months post-randomisation)
- Sleep quality(3 and 12 months post-randomisation)
- Reflux characteristics(3 and 12 months post-randomisation)
- Participant acceptability(12 months post-randomisation)
- Risk of sleep apnoea(12 months post-randomisation)
- Progression free survival(12 months post-randomisation)
- Hospital-free survival defined as death(12 months post-randomisation)
- Respiratory related hospital free survival(12 months post-randomisation)
- The decline and rate of decline in absolute %FVC(Measured over the course of 12 months)