Improvement of pain and quality of life in patients with sickle cell disease with overnight oxygen therapy or auto-adjusting positive airway pressure (APAP)

ISRCTN	ISRCTN46078697
DOI	https://doi.org/10.1186/ISRCTN46078697
Clinical Trials Information System (CTIS)	2014-002181-67
Protocol serial number	RHMCHI0706
Sponsor	University Hospital Southampton NHS Foundation Trust (UK)
Funder	National Institute for Health Research (NIHR) (UK) - CCR- RfPB grant

Submission date: 03/06/2014
Registration date: 18/07/2014
Last edited: 04/03/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Sickle cell disease (SCD) is an inherited blood disorder where the red blood cells do not develop normally. Instead of being flexible and disc-shaped like normal blood cells, they are rigid and shaped like a crescent (or sickle). They also contain defective haemoglobin, the iron-rich protein that enables red blood cells to carry oxygen. This results in lower than normal oxygen levels in the tissues and organs of the body and can cause people to feel lethargic (lack of energy), tired and breathless, particularly after exercise. Many complications of the condition are thought to be caused by low daytime and night time oxygen levels. These can be made worse if the patient also suffers from obstructive sleep apnoea (OSA) where the muscles and soft tissues in the windpipe relax and collapse during sleep, causing a total blockage of the airway; this results in an extra dip in oxygen levels during sleep. Overnight oxygen is already used in patients with chronic lung disease who suffer from low oxygen levels during sleep. Automatic positive airway pressure (APAP) machines, which work by blowing air at a pressure that keeps the windpipe open, are used successfully for OSA patients of all ages. It is possible that these treatments may also help people suffering from SCD. Early studies have shown that SCD patients do find overnight oxygen safe and easy to use. There is also some evidence that APAP can be beneficial to children with SCD, resulting in improved attention span and fewer crises. However, further work is needed to decide whether the inconvenience of these treatments outweigh any benefits from using them for treating dips in night time oxygen levels for SCD patients. The aim of this small scale (pilot) study is to find out which intervention (the overnight oxygen or APAP) is the most acceptable for patients by asking them to use them for one week each and then have an interview describing their experience. The most acceptable intervention will then be used for further study.

Who can participate?
English speaking SCD patients aged over 8 years and who are able to (or their parents are able to) use a smart phone.

What does the study involve?
Participants are first asked to fill in a daily pain diary for a week. They are then are randomly allocated to receive one of the two interventions. A sleep physiotherapist sets up the intervention and shows the participant how to use it. The participant them uses the intervention for a week, filling in their pain diary daily and will have phone interviews to discuss any symptoms suffered. After the seven day treatment, the intervention is stopped and the participant attends hospital for a review, which includes having blood and urine tests taken, and having their lung function and oxygen levels measured. Afterwards, the participant continues to fill in their pain diary for another week before repeating the procedure with the second intervention.

What are the possible benefits and risks of participating?
Participants may find that their condition improves from one or both interventions given in this trial. If this proves to be the case, we will leave the machine that provides the most benefit with the patient (with approval from their doctor). As regards to risks, some people may find the tests to check lung function uncomfortable and may make them feel dizzy. Blood tests can also be slightly painful. Overnight APAP and oxygen therapies may also be uncomfortable and inconvenient to the participant. There is evidence that higher doses of oxygen can stop new red blood cells from being made, but not with the doses and timing of the oxygen being used for this study.

Where is the study run from?
University Hospital, Southampton (UK)
Guy's and St Thomas' NHS Foundation Trust (UK)
UCL Institute of Child Health (UK)

When is the study starting and how long is it expected to run for?
July 2014 to December 2014

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Professor Fenella Kirkham
Fenella.Kirkham@ucl.ac.uk

Contact information

Prof Fenella Kirkham
Scientific

University Hospital Southampton
Child Health
Tremona Road
Southampton
SO16 6YD
United Kingdom

Phone	+44 (0)23 8120 4765
Email	Fenella.Kirkham@ucl.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial. Block randomisation by an independent statistician at RDS Southampton.
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Prevention Of Morbidity in Sickle cell disease 2a - pilot phase (POMS 2a): Improvement of pain and quality of life in patients with sickle cell disease with nocturnal oxygen therapy or auto-adjusting continuous positive pressure: pilot phase
Study acronym	POMS
Study objectives	The principal research question is to assess whether APAP or overnight oxygen therapy is more acceptable to patients and to assess whether there are any physiological effects of either therapy. This information will influence the choice of intervention in a second, proof of concept trial.
Ethics approval(s)	NRES Committee East of England - Cambridge South, 03/06/2014, ref: 14/EE/0163
Health condition(s) or problem(s) studied	Sickle Cell Disease
Intervention	Participants will have two interventions, APAP and overnight oxygen, for a week each in randomized order (week 2 and 4). There will be a week of baseline data collection (week 1), and a week of washout between the interventions (week 3).
Intervention type	Device
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	Patient feasibility, acceptability and preference will be explored using qualitative interviews
Key secondary outcome measure(s)	1. Pain: Using available Smartphone technology, information on: 1.1. Pain characteristics (intensity, location, quality) 1.2. Pain medications and non-pharmacological strategies used for pain 1.3. Healthcare visits will be collected in the pilot to test out the methodology and to determine whether there is any obvious effect of either intervention or its withdrawal, particularly if detrimental. This is important as the first outcome measure for trial 2b will be average pain intensity during the two observation periods. 2. Adverse events: The Clinical Report Forms (CRFs) for reporting adverse events will be trialed during this pilot to show efficacy in recording and reporting adverse events. 3. Daytime oxygen saturation will be collected before and after each intervention to determine whether there is any obvious effect of either intervention or its withdrawal, particularly if detrimental. 4. Lung volume will be collected before and after each intervention to determine whether there is any obvious effect of either intervention or its withdrawal, particularly if detrimental.
Completion date	01/12/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	20
Total final enrolment	21
Key inclusion criteria	1. Age over 8 years 2. Informed consent with assent in accordance with the institutional policies (UK ethical committee) and European or US Federal guidelines 3. Sickle cell haemoglobin (HbSS) diagnosed by standard techniques 4. Able to speak and understand English 5. Patient or parent/guardian able to use smart phone
Key exclusion criteria	1. Patient already on overnight respiratory support or has used it in the past 2. Hospital admission for acute sickle complication within the past 1 month 3. Patient with > 6 admissions for acute sickle complications within the past 12 months 4. Existing Respiratory Failure 5. Decompensated Cardiac Failure 6. History of Severe Epistaxis 7. Transsphenoidal
Date of first enrolment	01/07/2014
Date of final enrolment	01/12/2014

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

University Hospital Southampton

Southampton
SO16 6YD
United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London
-
United Kingdom

UCL Institute of Child Health

London
-
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	18/07/2019	04/03/2021	Yes	No
Protocol article	protocol	25/08/2015		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

04/03/2021: Publication reference and total final enrolment added.
21/11/2018: No publications found, verifying study status with principal investigator.