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Trial registered on ANZCTR


Registration number
ACTRN12616000617460
Ethics application status
Approved
Date submitted
4/05/2016
Date registered
12/05/2016
Date last updated
31/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
What is the safety and effectiveness, acceptability and cost of flexible delivery of natalizumab (Tysabri (Registered Trademark)) by nurses for people with multiple sclerosis?
Scientific title
What is the safety and clinical effectiveness, acceptability and cost effectiveness of flexible delivery of natalizumab (Tysabri (Registered Trademark)) by ambulatory care nurses for people with multiple sclerosis?
Secondary ID [1] 289130 0
(Clinical Trial Notification) CT-2016-CTN-02067-1 v1
Universal Trial Number (UTN)
Trial acronym
HiT (Home infusions of Tysabri)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
relapsing-remitting multiple sclerosis (MS) 298615 0
Condition category
Condition code
Neurological 298689 298689 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects in the treatment group will receive three 300mg natalizumab infusions occurring once every 4 weeks flexibly (either at home or in a workplace) from a Tysabri Australasian Prescribing Program (TAPP) trained ambulatory care nurse (level 3 RN). After three infusions in Phase 1 (lasting three months), subjects will cross over to the control group in Phase 2 and receive usual care for another three infusions (lasting three months). Crossover will therefore occur between the third and fourth infusions.
Intervention code [1] 294639 0
Treatment: Drugs
Intervention code [2] 294660 0
Treatment: Other
Comparator / control treatment
Subjects in the control group will receive usual care comprising three 300mg natalizumab infusions occurring once every 4 weeks in a hospital ambulatory day care unit by an infusion nurse. After three infusions in Phase 1 (lasting three months), subjects will cross over to the treatment group in Phase 2 and receive flexible delivery for another three infusions (lasting three months). Crossover will therefore occur between the third and fourth infusions.
Control group
Active

Outcomes
Primary outcome [1] 298175 0
Adverse events (number, severity, treatment patterns and patient outcomes) collected by nurses administering natalizumab infusions and self reported by patients. Known common adverse events include: headache, fever and chills, back pain, fatigue, rigors, nausea and localized or multi-symptomatic hypersensitivity reactions. These would be criteria for stopping the infusion if the patient has NOT experienced them before & seeking guidance from the consultant neurologist. More concerning adverse events that require immediate intervention and would require anaphylaxis management have symptoms including itching, dizziness, fever, rash, nausea, flushing, breathing trouble, and chest pain.
Timepoint [1] 298175 0
For both intervention and control groups, monitoring for adverse events by nurses will occur during the infusion and for one hour post-infusion. Patients will be able to record adverse events occurring outside of these times using a patient diary.
Secondary outcome [1] 323378 0
Infections (a composite outcome comprising number; type, including whether hospital acquired; treatment) recorded by both patients and nurses administering natalizumab.
Timepoint [1] 323378 0
For both intervention and control groups, monitoring for will occur during the monthly infusion. Patients will be able to record infections occurring outside of these times using a patient diary.
Secondary outcome [2] 323379 0
Patient satisfaction with their treatment using the ‘Treatment Satisfaction Questionnaire for Medication’ (TSQM)’
Timepoint [2] 323379 0
Patient satisfaction will be measured at the end of phase 1 (at 3 months) and phase 2 (at 6 months) in both study arms.
Secondary outcome [3] 323380 0
Quality of life using the MS Quality of Life Inventory (MSQLI) a battery of measurements consisting of 10 individual scales providing a quality of life measure that is both generic and MS-specific.
Timepoint [3] 323380 0
Quality of life will be measured at baseline (before trial commences), and at the end of phase 1 (at 3 months) and phase 2 (at 6 months) in both study arms.
Secondary outcome [4] 323381 0
Expanded Disability Status Scale (EDSS) measured by a neurologist.
Timepoint [4] 323381 0
EDSS will be measured at baseline (before trial commences), and at the end of phase 1 (at 3 months) and phase 2 (at 6 months) in both study arms.
Secondary outcome [5] 323382 0
Treatment adherence -assessed as the proportion of completed treatments from the total number of eligible treatments.
Timepoint [5] 323382 0
Treatment adherence will be measured at the end of phase 1 (at 3 months) and phase 2 (at 6 months) in both study arms.

Eligibility
Key inclusion criteria
To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of randomization:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Being prescribed natalizumab
3. have been risk assessed as safe for the flexible infusion delivery program by the prescribing Neurologist
4. the patient has had a minimum of 6 natalizumab infusions in an infusion service unit (e.g. Royal Adelaide Hospital)
5. JCV negative (this will be re-tested at 6 monthly intervals)
6. comply with other vigilance requirements – MRI, bloods etc.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of randomization:
1. Unable or unwilling to provide informed consent.
2. MS patients 17 years or younger
3. Have received less than 6 infusions in an infusion service unit
4. the patient is deemed unsafe for the flexible infusion delivery program by the prescribing Neurologist.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone to study coordinator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Study coordinator will use a random numbers table and block randomisation to ensure equal numbers in the control and intervention groups.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
The study will test for equivalence in the delivery of natalizumab flexibly and at hospital outpatients department. The goal of an equivalence study is to demonstrate equivalency between two treatments, i.e. that the efficacies of two treatments are close enough so that one cannot be considered superior or inferior. Therefore, in equivalence studies, the null hypothesis is that the two treatments are not equivalent, and if the null hypothesis is rejected, the alternate hypothesis of equivalence between the two treatments is supported.
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
In general, the analysis will be based on within-subjects comparisons between the two study time periods, as all participants will be exposed to both the control and intervention.
The analysis will include tests for confounding due to treatment effects or period effects to rule out a carryover effect (i.e. the washout phase between A/B and B/A was not long enough).

Depending on the frequency of events, variables measured by counts (adverse drug events) may be analysed as continuous data, Poisson-distributed count data or dichotomous data. For continuous and Poisson distributions, t-tests will be used, in the latter chi-square tests would be used. The treatment adherence will be tested using a comparison of proportions.

Outcomes that are measured before (‘pre’) and after (‘post’) each phase (i.e. quality of life via MSQLI and EDSS) the differences between pre-post measures will be calculated and compared between treatment and control interventions using univariable analysis (eg t-tests). Multivariable analysis adjusting for potential co-variates based on patient demographics (eg age, gender, length and severity of the disease) will also be conducted.

For continuous outcomes (e.g. satisfaction scores) that are measured only once at the end of each phase, unpaired t-tests will be conducted on the within subject differences.

The significance level will be set at a=0.05.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 5722 0
The Royal Adelaide Hospital - Adelaide

Funding & Sponsors
Funding source category [1] 293500 0
Commercial sector/Industry
Name [1] 293500 0
Biogen Australia and New Zealand
Address [1] 293500 0
Level 3, 123 Epping Rd. North Ryde NSW 2113 Australia
Country [1] 293500 0
Australia
Primary sponsor type
Individual
Name
Dr Janakan Ravindran
Address
Royal Adelaide Hospital, North Tce, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 292329 0
Individual
Name [1] 292329 0
Dr Tim Schultz
Address [1] 292329 0
School of Nursing, University of Adelaide, North Tce, Adelaide, SA 5000
Country [1] 292329 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294942 0
Royal Adelaide Hospital HREC
Ethics committee address [1] 294942 0
North Tce Adelaide SA 5000
Ethics committee country [1] 294942 0
Australia
Date submitted for ethics approval [1] 294942 0
04/05/2016
Approval date [1] 294942 0
22/06/2016
Ethics approval number [1] 294942 0
HREC/16/RAH/192

Summary
Brief summary
In some countries (eg Canada and UK), some patients can receive monoclonal antibody (MAB) treatment at home, under the supervision of an appropriately trained registered nurse. However, we are not aware of any comparable studies examining the safety of natalizumab and flexible delivery (i.e. treatment at home, or in a community setting) for people with multiple sclerosis (MS).

Therefore, the broad objective of this study is to investigate the flexible delivery of natalizumab. In many cases, it is anticipated that flexible delivery will entail delivery in the patient’s own home. The study will compare the flexible delivery of natalizumab with usual care (attendance in an outpatient department) and answer whether it is acceptable to patients, is effective and safe, and is cost effective. The study will comprise a pilot study to better understand feasibility and safety, and to inform a larger, proposed full-scale study.

The primary objective of the study is to determine whether the flexible delivery of natalizumab is safe for people with MS. The additional objectives of this study in this study population are as follows:
(a) Is the flexible delivery of natalizumab acceptable to patients and healthcare staff?
(b) Is the flexible delivery of natalizumab as effective in treating symptoms?
(c) Is the flexible delivery of natalizumab cost effective?
Trial website
n/a
Trial related presentations / publications
n/a
Public notes

Contacts
Principal investigator
Name 65586 0
Dr Janakan Ravindran
Address 65586 0
Royal Adelaide Hospital, North Tce, Adelaide, SA 5000
Country 65586 0
Australia
Phone 65586 0
+618 8222 2172
Fax 65586 0
Email 65586 0
Janakan.Ravindran@sa.gov.au
Contact person for public queries
Name 65587 0
Dr Tim Schultz
Address 65587 0
School of Nursing, University of Adelaide, North Tce, Adelaide, SA 5000
Country 65587 0
Australia
Phone 65587 0
+618 8313 6270
Fax 65587 0
Email 65587 0
tim.schultz@adelaide.edu.au
Contact person for scientific queries
Name 65588 0
Dr Janakan Ravindran
Address 65588 0
Royal Adelaide Hospital, North Tce, Adelaide, SA 5000
Country 65588 0
Australia
Phone 65588 0
+618 8222 2172
Fax 65588 0
Email 65588 0
Janakan.Ravindran@sa.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary