Extracorporeal Photopheresis (light treatment of white blood cells) in the treatment of Chronic Lung Allograft Dysfunction (chronic rejection): a randomised controlled trial

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 90

Inclusion Criteria

1. Adults (=16 years of age) with body weight =30 kg
2. Bilateral lung or heart and (bilateral) lung transplant recipients
3. Confirmed diagnosis of CLAD stages 1, 2 or 3 as per ISHLT 2019 consensus definition
4. New CLAD diagnosis or prior diagnosis with evidence of current progressive disease
5. Exclusion of non-CLAD causes for decline in lung function by high-resolution computed tomography (HRCT) thorax and bronchoscopy +/- transbronchial biopsy within 12 weeks of first CLAD diagnoses
6. Adequate treatment of potential non-CLAD causes of a decline in lung function (e.g. acute cellular or acute humoral rejection, infections, airway anastomotic strictures and medical treatment for gastroesophageal reflux)
7. =3 recorded FEV1 and FVC measurements including home spirometry obtained at intervals of =3 weeks during the 26 weeks preceding randomisation
8. Progressive decline in FEV1 (=10%) while on azithromycin for =6 weeks
9. Capacity to provide written informed consent

Exclusion Criteria

1. Single lung transplant recipients
2. Female patients who are breastfeeding, pregnant or planning to become pregnant during the timeframe of study participation
3. Current treatment with or past history of TLI completed within the last 12 months
4. =1-month wash-out from any other investigational therapies for CLAD
5. Inability to perform lung function tests or adhere to study protocol as judged by supervising clinician
6. History of Hematopoietic Stem Cell Transplantation (HSCT)
7. Patients who are on a retransplant waiting list
8. Current participation in another interventional clinical trial, or participation in a clinical trial of an investigational agent in the previous 4 weeks from consent
9. Patients with inadequate vascular access options to perform ECP
10. Any contraindication to receiving ECP. These include:
10.1. Previous allergic reaction to Methoxsalen, another psoralen compound, or any of the other UVADEX® ingredients
10.2. Co-existing untreated skin cancer (melanoma, basal cell or squamous cell cancer) if the patient deemed at higher risk of harm due to exposure to UVADEX or from their CLAD diagnosis
10.3. Any disease which involves sensitivity to light such as porphyria, systemic lupus erythematosus or albinism
10.4. Previous removal of spleen
10.5. Blood clotting disorder or an increased white blood cell count >25 x 10e9 per litre
10.6. Significant heart disease or severe anaemia causing inability to tolerate blood volume shifts associated with ECP
10.7. Aphakia or lens removed from either eye (unless already blind in eye without a lens)
10.8. Sexually active men and women of childbearing potential unless adequate contraception is used during treatment

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
ung function stabilisation is measured using change in FEV1 and FVC at 12 and 24 weeks compared to baseline at study entry

Secondary Outcome Measures

Name	Time	Method
1. Rate of decline in lung allograft function measured using spirometry (FEV1 and FVC) at baseline and 24 weeks<br>2. Exercise capacity measured using distance walked in the 6 Minute Walk Test at baseline and 24 weeks<br>3. Disease severity measured by CLAD classification as per ISHLT guideline at baseline and 24 weeks<br>4. Health-related quality of life measured by the SF-36 v2 and EQ-5D-5L questionnaires at baseline and 24 weeks<br>5. Survival collected from medical records at 24 weeks<br>6. Safety measured by collecting details of adverse events and serious adverse events occuring between baseline and 24 weeks