Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04560699 |
| Other study ID # |
APPI2-PT-2020-AIMSS |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 14, 2020 |
| Est. completion date |
April 4, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Frederiksberg University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The primary objective of this trial is to assess the efficacy of targeted individualised
physiotherapeutic treatment on aromatase inhibitor-associated musculoskeletal pain.
This trial asks a critical, previously unaddressed, question of clinical importance about
management of musculoskeletal (MSK) pain secondary to aromatase inhibitor (AI) treatment of
hormone receptor-positive breast cancer. Many breast cancer survivors taking AIs experience
muscle and/or joint pain, which may cause many to stop taking AIs and may inhibit exercise or
physical activity, despite its known health benefits.
Physiotherapeutic treatment is considered a standard management strategy for many MSK pain
conditions, in which targeted specific exercise therapy is now as an evidence-based
management strategy with proven effectiveness and patient satisfaction. Thus, referral to
physiotherapy would be a natural strategy in women who experience MSK pain as an adverse
effect to AI therapy. However, it is unclear if physiotherapeutic treatment has similar
effects on AI induced MSK pain as in primary MSK pain. Two systematic review (one with a
meta-analysis) have assessed the effect of different pain management strategies for
AI-induced MSK-pain and found great uncertainty in the effects of exercise, relaxation
techniques and acupuncture. They also found limited evidence on the subject and moderate to
low quality of the studies included. The evidence on the subject is clearly limited but the
need for a treatment option to minimize the side-effects of the AI medication real and
necessary.
Targeted individualised physiotherapeutic treatment is tailored for the affected (painful)
tissue/joint/region specifically and is based on extensive experience and evidence from MSK
physiotherapy in rheumatic and orthopedic patient population. Targeted individualised
physiotherapy treatment take into account the individual patient, her constitution, the
painful tissue/region/joint (e.g. its biomechanics, physiological properties, and
inflammatory activity), and is adjusted according to day-to-day variations in pain and
progressed based on the interaction between changes in symptoms and function and tissue
healing. Such approach is expected to yield a greater effect on MSK pain, than a generic
exercise program. Further, targeted treatment programs are delivered by trained
physiotherapists, who have specific clinical training and experience in clinical management
of patient and handling MSK pain, which is also expected to yield better clinical outcomes
than programs delivered by people without clinical training.
Altogether it is very likely that a targeted physiotherapy treatment will be of significant
benefit to breast cancer survivors with AI induced MSK pain.
The aim is to compare targeted individualized physiotherapeutic treatment and medical care
with medical care alone on aromatase inhibitor associated musculoskeletal pain in female
breast cancer survivors.
It is hypothesized that targeted physiotherapeutic treatment and medical care reduces
musculoskeletal pain significantly in women with aromatase inhibitor associated
musculoskeletal pain when compared to medical care alone.
The plan is to include 120 participants from the oncology department at Rigshospitalet,
Denmark.
Participants will partake in the study for a total of 26 weeks. During the first 12 week the
intervention group will receive the physiotherapeutic treatment twice a week. The medical
care visits are place at the first visit to the clinic, week 13 and week 26.
Description:
The primary objective of this trial is to assess the efficacy of targeted individualised
physiotherapeutic treatment on aromatase inhibitor-associated musculoskeletal pain.
This trial asks a critical, previously unaddressed, question of clinical importance about
management of musculoskeletal (MSK) pain secondary to aromatase inhibitor (AI) treatment of
hormone receptor-positive breast cancer. Many breast cancer survivors taking AIs experience
muscle and/or joint pain, which may cause many to stop taking AIs and may inhibit exercise or
physical activity, despite its known health benefits.
Physiotherapeutic treatment is considered a standard management strategy for many MSK pain
conditions, in which targeted specific exercise therapy is now as an evidence-based
management strategy with proven effectiveness and patient satisfaction. Thus, referral to
physiotherapy would be a natural strategy in women who experience MSK pain as an adverse
effect to AI therapy. However, it is unclear if physiotherapeutic treatment has similar
effects on AI induced MSK pain as in primary MSK pain. Two systematic review (one with a
meta-analysis) have assessed the effect of different pain management strategies for
AI-induced MSK-pain and found great uncertainty in the effects of exercise, relaxation
techniques and acupuncture. They also found limited evidence on the subject and moderate to
low quality of the studies included. The evidence on the subject is clearly limited but the
need for a treatment option to minimize the side-effects of the AI medication real and
necessary.
Targeted individualised physiotherapeutic treatment is tailored for the affected (painful)
tissue/joint/region specifically and is based on extensive experience and evidence from MSK
physiotherapy in rheumatic and orthopedic patient population. Targeted individualised
physiotherapy treatment take into account the individual patient, her constitution, the
painful tissue/region/joint (e.g. its biomechanics, physiological properties, and
inflammatory activity), and is adjusted according to day-to-day variations in pain and
progressed based on the interaction between changes in symptoms and function and tissue
healing. Such approach is expected to yield a greater effect on MSK pain, than a generic
exercise program. Further, targeted treatment programs are delivered by trained
physiotherapists, who have specific clinical training and experience in clinical management
of patient and handling MSK pain, which is also expected to yield better clinical outcomes
than programs delivered by people without clinical training.
Altogether it is very likely that a targeted physiotherapy treatment will be of significant
benefit to breast cancer survivors with AI induced MSK pain.
The aim is to compare targeted individualized physiotherapeutic treatment and medical care
with medical care alone on aromatase inhibitor associated musculoskeletal pain in female
breast cancer survivors.
It is hypothesized that targeted physiotherapeutic treatment and medical care reduces
musculoskeletal pain significantly in women with aromatase inhibitor associated
musculoskeletal pain when compared to medical care alone.
The plan is to include 120 participants from the oncology department at Rigshospitalet.
Participants will partake in the study for a total of 26 weeks. During the first 12 week the
intervention group will receive the physiotherapeutic treatment twice a week. The medical
care visits are place at the first visit to the clinic, week 13 and week 26.
Allocation of participants and sequence generation The randomization list will be
computer-generated based upon permuted random blocks of variable size (4 to 6 in each block).
The allocation ration will be 1:1 (1 targeted physiotherapeutic treatment (TPT)+ medical care
(MC) for each 1 MC) stratified according to upper or lower MSK pain site.
The biostatistician or his delegate will develop the randomisation scheme for allocation
subjects to the two treatment arms.
Investigators, study coordinators, clinical staff, study staff, and other personnel directly
involved in the study, will be blinded to the group allocation.
Participants and staff involved in the physiotherapy treatment are not blinded to the group
allocation. Information that could potentially unblind otherwise blinded staff will not be
shared, and will be stored in facilities with limited access until the study is completed.
Unblinding of blinded personnel does not preclude the related participants' continued
participation in the study.
Attendance to the physiotherapy sessions and the medical doctor appointments will be recorded
in the case report form (CRF).
The investigator and clinical staff will monitor each participant for evidence of adverse
events (AEs) throughout the study. The investigator will assess and record any AE in detail
including the date of onset, description, severity, duration and outcome, relationship of the
AE to study treatment, and any action(s) taken. AEs, whether in response to a query, observed
by site personnel, or reported spontaneously by the participant will be recorded.
A participant may withdraw from the study at any time without this impacting on any future
investigations and/or treatments at the site, by the Investigators in this study or by other
staff associated with the study.
If a participant withdraws from the study, the procedures outlined for the closest assessment
visit is sought to be completed within 2 weeks, and preferably prior to the initiation of
another therapy. However, these procedures should not interfere with the initiation of any
new treatments or therapeutic modalities that the investigator feels are necessary to treat
the participant's condition.
All AEs will be followed to a satisfactory conclusion. The investigator may discontinue any
participant's participation for any reason, including an AE, safety concerns or failure to
comply with the protocol.
Participants will be discontinued from the study immediately if any of the following occur:
- Clinically significant abnormal laboratory results or AEs, which rule out continuation
of the study treatment, as determined by the investigator
- Death
- Other illness
- Failure to adhere to the protocol
If at any point in time between randomization and the week-26 visit the investigator feels
that the patient's clinical course is not acceptable within the normally applied paradigms of
AIMSS, the patient should be taken out of the study. The clinician's judgment will be
required to decide on a case-by-case basis whether to implement this step or not.
It is important to avoid any loss to follow-up participants for the efficacy assessment and
meaningful analysis of the study.
The principal investigator has the right to terminate this study at any time. Reasons may
include the following, but are not restricted to:
- The incidence of events in this or other studies that indicate a potential health hazard
to participants.
- Unsatisfactory participant enrolment. Determination of Sample Size This is a superiority
study with the main outcome being change in pain from baseline to end of study (week
13), measured with the BPI.
Given a standard deviation of 2.5 a total sample size of 100 is required to obtain a power of
0.85 (actual power is 0.887) to detect a mean group difference in the change from baseline of
1.5 points at a significance level of 0.05 and using a balanced design (1:1 randomization).
Allowing for drop-outs the study aims at recruiting and randomize 120 participants, which
would yield a power of 0.935 to detect the above difference at the 0.05 level of
significance.
Power and sample size analyses were conducted using 'SAS Power and Sample Size' (SAS
Institute Inc., Cary, North Carolina).
Disposition of participants The number of randomized patients will be summarized as total
using counts and percentages. The number of patients either completing or permanently
discontinuing the study will be summarized using counts and percentages.
For the assessment of superiority, the intention-to-treat (ITT) protocol population is used
in the primary analysis, as it is the most conservative approach.
The ITT population consist of all randomized patients irrespective of whether the patient
actually received study intervention or the patient's compliance with the study protocol, in
the treatment group to which the participant was assigned at randomisation. A patient will be
considered randomised as soon as a treatment is assigned by according to the allocation
sequence.
A statistical analysis plan that describes the details of the planned statistical analyses
will be produced by the principal investigator and a biostatistician or his delegate before
last patient's last visit.
Assessments of changes from baseline and construction of confidence intervals (CI) for
continuous measures will be based on a repeated measures analysis of covariance (ANCOVA;
including group as the main factor and baseline measure as covariate).
Superiority will be claimed if the computed 95% confidence interval of the estimated group
difference in the change from baseline in the BPI does not include 0 in the ITT population.
All statistical tests will be two-sided and statistical significance will be claimed if the
computed p-value is equal to or less than 0.05.
The study will use paper case report forms (CRF) and an in-house custom built electronic data
capture system (Cirkeline) and REDCap (internet survey system for the 6-week assessment).
Paper based CRF allows for on the go registration of participation in the TPT + MC group as
well as registration from the structured interview.
Cirkeline allows individual patients to supply questionnaire data at clinical visits via
touch-screens in the clinic, as well as entering of study related data by the staff.
REDCap allows the participants to fill out the questionnaires from home via a secure web
browser.
At the end of the trial, all data will be merged and stored in a database created by the
Parker Institutes database manager.
The applications meet all regulatory standards and allow management of all activities related
to clinical trials that ensures optimal resource use and safety according to good clinical
practice and data protection legislation.
Regulatory Standards Participant confidentiality Participant medical information obtained by
this study is confidential, and disclosure to third parties other than those noted below is
prohibited.
With the participant's permission, medical information may be shared with his or her personal
physician or with other medical personnel responsible for the participant's welfare.
If the data from this study are published, the presentation format will not include names,
recognizable photos, personal information or other data which compromises the anonymity of
participating participants.
The study will be conducted in accordance with the Data Protection Act and follow the General
Data Protection Regulation. The study data management and data security procedures is
approved by the Regional Knowledge Centre on Data Protection Compliance on behalf of the
Danish Data Protection agency.
All data will be entered into a study database for analysis and reporting. Any data captured
electronically will be stored electronically in a separate database according to standard
procedures at The Parker Institute. Upon completion of data entry, the databases will be
checked to ensure acceptable accuracy and completeness. System backups and record retention
for the study data will be consistent with The Parker Institute standard procedures.
Individuals involved in study evaluations will be trained to perform the efficacy and safety
evaluations described in the protocol.
The study has received funding from Danish Physiotherapists Association and The Oak
Foundation (OCAY-13-309; covering running cost at the Parker Institute including this study),
for the specific purpose to complete this study. None of the investigators have conflicts of
interests related to the funding of this study. This information is disclosed to all
participants in the written information material.
All sources of support (including technical and financial support) provided for this study is
disclosed in the written information material and in publication of the study results.
Funding is an ongoing process. All future financial and/or technical support to the study
will be reported to the Danish health research ethical committee system and is disclosed to
all participants (previous, current and potential).
The participants are insured by the Danish Patient Insurance Association.
