Cytomegalovirus (CMV) in allogeneic hematopoietic stem cell transplant patients

ISRCTN	ISRCTN78128786
DOI	https://doi.org/10.1186/ISRCTN78128786
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	287712
Protocol serial number	TAK620-5002, IRAS 287712, CPMS 46626
Sponsor	Takeda (United States)
Funder	Takeda Pharmaceuticals U.S.A.

Submission date: 29/09/2021
Registration date: 25/11/2021
Last edited: 24/08/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Cytomegalovirus (CMV) is one of the most common infections that affects people with an allogeneic hematopoietic stem cell transplant (HSCT). Allogeneic stem cell transplantation involves transferring stem cells from a healthy person to the patient’s body after high-intensity chemotherapy or radiation. The aim of this study is to describe the treatment patterns and outcomes of CMV in about 400 HSCT recipients globally who required treatment for the management of CMV.

Who can participate?
Records from patients who were over 18 years old at the time of their HSCT and who were then treated for a CMV infection

What does the study involve?
The study will use the healthcare information that has already been documented from 1 January 2014 (until no later than determined at site level) related to the HSCT, CMV infections and outcomes including hospital visits, clinic visits, written follow-up notes, drug treatments, tests and procedures. This observational study uses records from routine healthcare, so the results of the study are not expected to be directly or immediately relevant to patient care and will not be shared with each participant.

What are the possible benefits and risks of participating?
This is a retrospective observational study so there are no physical risks that will result from taking part in this study. Taking part in this study has a very low risk of personally identifying information (PII) being accessed by unauthorized people (i.e., individuals who are not part of the study team). To reduce the risk of sharing PII with unauthorized persons, patient identifiers will be removed before being used in research so as to maintain confidentiality and privacy protection. It is expected there will be limited or no direct or immediate benefit to participants.

Where is the study run from?
Shire Human Genetic Therapies, Inc. a wholly-owned subsidiary of Takeda Pharmaceutical Company Ltd (USA)

When is the study starting and how long is it expected to run for?
May 2019 to December 2021

Who is funding the study?
Shire Human Genetic Therapies, Inc. a wholly-owned subsidiary of Takeda Pharmaceutical Company Ltd (USA)

Who is the main contact?
Ishan Hirji, Ishan.hirji@takeda.com

Contact information

Ms Ishan Hirji
Public

650 E. Kendall Street
Cambridge, MA
02142
United States of America

Phone	+1 (0)6175888190
Email	ishan.hirji@takeda.com

Ms Ishan Hirji
Scientific

650 E. Kendall Street
Cambridge, MA
02142
United States of America

Phone	+1 (0)6175888190
Email	ishan.hirji@takeda.com

Study information

Primary study design	Observational
Study design	Multinational non-interventional retrospective study
Secondary study design	Retrospective study
Study type	Participant information sheet
Scientific title	Multinational CMV Outcomes, Treatment Patterns and Healthcare Resource Utilization Study following Hematopoietic Stem Cell Transplant (OTUS HSCT)
Study acronym	OTUS HSCT
Study objectives	Primary objective: To evaluate and describe the clinical outcomes with current management patterns Secondary objectives: 1. To describe the treatment patterns of cytomegalovirus (CMV) management 2. To describe the patient/clinical characteristics of Hematopoietic Stem Cell Transplant (HSCT) recipients 3. To describe the economic burden and healthcare resource utilization
Ethics approval(s)	Approved 11/12/2020, HRA and Health and Care Research Wales (Castlebridge 4, 15 - 19 Cowbridge Rd E, Cardiff, CF11 9AB, UK; +44 (0)2920 230457; HCRW.approvals@wales.nhs.uk); REC ref: 20/LO/1105
Health condition(s) or problem(s) studied	Cytomegalovirus infection in transplanted patients
Intervention	The study will use the healthcare information that has already been documented from 1 January 2014 (until no later than determined at site level) related to the HSCT, CMV infections and outcomes including hospital visits, clinic visits, written follow-up notes, drug treatments, tests and procedures. This observational study uses records from routine healthcare.
Intervention type	Other
Primary outcome measure(s)	1. Number of CMV viremia episodes measured using patient records from transplant date until the end of follow-up 2. Time from HSCT to CMV viremia measured using patient records 3. Time to CMV viremia clearance measured using patient records 4. Incidence and time to CMV recurrence measured using patient records from CMV index episode until the end of follow-up 5. Incidence of tissue invasive disease measured using patient records from transplant date until the end of follow-up 6. Incidence of graft rejection measured using patient records from transplant date until the end of follow-up 7. Incidence of post-HSCT non-CMV infections requiring intravenous (IV) treatment or hospitalization, measured using patient records from transplant date to 365 days following the last PRRI CMV episode or until death (whichever occurs first) 8. Incidence of anti-CMV treatment-related myelosuppression, nephrotoxicity or other toxicities, measured using patient records from the first CMV episode until the end of follow-up 9. CMV resistance measured using patient records from the first CMV episode until the end of follow-up 10. CMV-associated mortality measured using patient records 11. All-cause mortality measured using patient records *Time of follow-up: at least 365 days after being designated as refractory, resistant or intolerant for the first time or until death, whichever comes first.
Key secondary outcome measure(s)	1. CMV prophylaxis and pre-emptive therapy, management of CMV reactivation/recurrence, measured from transplant date until the end of follow-up 2. Frequency of first-, second,- and third-line anti-CMV agents, measured using patient records from the first CMV episode until the end of follow-up 3. Time from HSCT to incident CMV-specific anti-viral therapy, measured using patient records 4. Viral load measured using patient records at transplant date and from 14 days prior to the start through the end of CMV episodes or until clearance 5. Medication utilization measured using patient records from transplant date until the end of follow-up 6. Demographics, diagnosis, transplant procedure, clinical, prior transplants, transplant indication, HCT comorbidity index comorbidities and score, prophylactic immunosuppressive regimen, measured using patient records at a pre-transplant time 7. Viral infections and prophylactic/treatment immunosuppressive regimen measured using patient records from transplant date until the end of follow-up 8. Viral infections, incidence and time to acute and chronic graft vs host disease (GVHD) and immunosuppressive regimen, measured using patient records from transplant date until the end of follow-up 9. Inpatient healthcare utilization, length of hospital stay, cause of hospitalization and number of outpatient clinic visits, measured using patient records from transplant date until the end of follow-up *Time of follow-up: at least 365 days after being designated as refractory, resistant or intolerant for the first time or until death, whichever comes first.
Completion date	06/12/2021

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	400
Total final enrolment	379
Key inclusion criteria	Cohort 1: Resistant/refractory/intolerant inclusion criteria: 1. Aged ≥18 years at the time of the HSCT 2. Received an HSCT after 1 January 2014 3. Diagnosed with CMV infection any time after the HSCT date 4. Characterized as resistant to currently available treatments, OR refractory to currently available treatments, OR considered intolerant to currently available treatments 5. Follow-up data are available for at least 12 months (1 year) after being characterized in item (4) (above) or until death, whichever occurs first Cohort 2: Pre-emptive treatment for CMV viremia inclusion criteria: 1. Aged ≥18 years at the time of the HSCT 2. Received an HSCT after 1 January 2017 3. Diagnosed with CMV viremia any time after the HSCT date 4. Received pre-emptive treatment 5. Follow-up data are available for at least 12 months (1 year) after being characterized in item (4) (above) or until death, whichever occurs first
Key exclusion criteria	Positive test for HIV before the HSCT
Date of first enrolment	16/10/2020
Date of final enrolment	30/11/2021

Locations

Countries of recruitment

United Kingdom
England
Wales
France
Germany
Italy
Spain
United States of America

Study participating centres

King's College Hospital

SE5 9RS
United Kingdom

Hospital Universitario La Fe

46026
Spain

Centre Hospitalier Lyon Sud

69495
France

Centre Hospitalier Universitaire de Limoges

87000
France

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto

60126
Italy

University Hospital Wurzburg

97080
Germany

University Hospital of Wales

CF14 4XW
United Kingdom

University College London Hospital

NW1 2PG
United Kingdom

Hospital Universitari General Vall d'Hebron

08035
Spain

Tufts Medical Center

02111
United States of America

Johns Hopkins University

21287
United States of America

Weill Cornell Medicine

10065
United States of America

Memorial Sloan Kettering Cancer Center

10065
United States of America

University Hospital Mainz

55131
Germany

University Hospital Dusseldorf

40225
Germany

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated and/or analysed during the study will be made available upon request to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Other unpublished results	Text-based summary of results	30/07/2023	24/08/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN78128786_Other unpublished results_30Jul2023.pdf: Text-based summary of results

Editorial Notes

24/08/2023: A text-based summary of results has been added.
25/01/2022: The following changes were made to the trial record:
1. The overall end date was changed from 30/12/2021 to 06/12/2021.
2. The total final enrolment was added.
07/12/2021: Internal review.
27/10/2021: Trial's existence confirmed by the London - Surrey Research Ethics Committee.