Effects on Muscle Strength After Blood Flow Restriction Resistance Exercise (BFR-RE) in Early In-patient Rehabilitation of Chronic Obstructive Pulmonary Disease Acute Exacerbation (COPDAE), a Single Blinded, Randomized Controlled Study
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease, Acute Exacerbation of COPD
Sponsor: Hospital Authority, Hong Kong

Study Protocol_v2_ updated on 8.7.2020 
 
 
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Title 
Effects on muscle strength after blood flow restriction 
resistance exercise (BFR-RE) in early in-patient rehabilitation 
of chronic obstructive pulmonary disease acute exacerbation 
(COPDAE), a single blinded, randomized controlled study 
 
 
 
NCT number: NCT04448236 
 
 
 
Last updated on 8th July, 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol_v2_ updated on 8.7.2020 
 
 
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Introduction 
Chronic obstructive pulmonary disease (COPD) is a prevalent disease around 
the world particularly in developed countries. COPD often has frequent 
admissions for acute exacerbation which increase the risks of mortality. 
Muscular dysfunction is one of extra-pulmonary morbidity of COPD (Jaitovich, 
2018). 
 
Reduced muscle strength is associated with increased mortality in moderate to 
severe COPD (Swallow, 2007). However, at least 70% of 1-repetiative 
maximum of weight is needed to achieve muscle growth in resistance training 
(ACSM, 2009). This might not be feasible particularly to the patients admitted 
for COPD acute exacerbation (COPDAE). 
 
Blood flow restriction resistance training (BFR-RE), Kaatsu training, was 
developed by Dr. Yoshiaki Sato more than 40 years ago (Sato, 2005). The 
basic physiological mechanism of BFR-RE to increase muscle mass and 
strength is by metabolite accumulation, e.g. lactate. The metabolites lead to 
increase of serum growth hormone (GH) which promotes the collagen 
synthesis for tissue repair and recovery. The surge of GH leads to release of 
insulin-like growth factor (IGF-1) which is a protein related to muscle growth. 
IGF-1 contributes the muscle gain, which is a muscular anabolic process, by 
enhancing satellite cell proliferation. (Manini, 2009) 
 
Concerning growth of muscle mass, BFR-RE leads to a comparable increase 
when compared to high load resistance exercise (HL-RE) (Lixandrão, 2017). 
However, concerning increase of muscle strength, BFR-RE is less effective in 
gain than that in HL-RE but more effective than that in low load resistance 
exercise (LL-RE) alone. Therefore, BFR-RE can be considered when HL-RE is 
not advisable. (e.g. frail elderly, post-operative rehabilitation, etc.) 
 
BFR-RE is well studied among healthy adult (Lixandrão, 2017), elderly 
(Centner, 2019) and musculoskeletal rehabilitation patients (Hughes, 2017), 
but not in COPDAE patients. 
Standardized isotonic knee extension resistance training on alternate day with 
a load of 15-30% of 1-repetition maximum (1-RM) with “BFR-device” will be 
compared with the control arm having same set of training without the device 
in COPDAE patient during 2-week of inpatient stay. 
 
Though there no adverse risk responses were reported in published 

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randomized controlled trials in clinical populations in the literature, there are 
some expected transient perceptual type responses, e.g. dizziness, limb 
numbness, perceived exertion, delayed onset muscle soreness. There are no 
significant risks of complications if BFR-RE is prescribed by certified trainers 
who have knowledge of appropriate protocols and contraindications to the use 
of occlusive stimuli. (Brandner, 2018) 
 
The effect on muscle strength in COPDAE inpatients, which is not well studied 
in the literature, will be the primary outcome of this study. The effect on mobility 
functions, systemic muscle strength reflected by hand grip strength, health 
related quality of life and unplanned readmission rate within 1 month of 
discharge for COPDAE will be evaluated as secondary outcomes. Since 
BFR-RE is newly introduced to Haven of Hope Hospital and not widely used in 
Hospital Authority, acceptability and feasibility of this training will be explored 
as secondary outcomes. 
 
Subjects 
Patients with COPD acute exacerbation (COPDAE) will be recruited to find out 
the effect of blood flow restriction resistance exercise (BFR-RE). There will be 
a control group without BFR-RE for comparison. Principal investigator will 
screen the medical fitness of the subjects before recruiting to the study. 
 
Inclusion criteria 
1. 
COPD acute exacerbation (COPDAE) as the primary diagnosis for 
hospitalization or transfer to pulmonary wards of the Haven of Hope 
Hospital 
2. 
Able to walk under supervision 
3. 
Understand instruction in Cantonese and can give informed consent. 
 
 
 
 
 
Exclusive criteria (Hick, 2013) 
Subjects will be excluded if they have any of the following conditions: 
1. 
Concomitant acute cardiac event 
2. 
Severe hypertension (BP > 
180/100) 
7. 
History of lymphectomies 
8. 
Extremities with dialysis access 
9. 
Vascular grafting 

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3. 
History of venous 
thromboembolism 
4. 
History of peripheral vascular 
disease 
5. 
Absence of posterior tibial or 
dorsalis pedal pulse 
6. 
History of revascularization of the 
extremity 
10. Current extremity infection 
11. Active malignancy* 
12. Open fracture / soft tissue injuries 
13. Amputation to the lower extremity 
14. Expected hospitalization less 
than 2 weeks on admission 
15. Medications known to increase 
clotting risks 
16. Isolation / Contact precaution 
requirement (e.g. MRSA status, 
CD toxin +ve status, etc.) 
 
*Active malignancy (Kearon,2016) is defined as follow: 
(1)  not received potentially curative treatment; or  
(2)  there is evidence that the treatment has not been curative (e.g. 
recurrent or progressive disease); or 
 
A treated cancer is cured should be made by an experienced 
clinician, with the decision requiring a disease-free interval of 
follow-up.  
(3)  treatment is ongoing.  
 
Standardized 2-week in-patient rehabilitation 
 Breathing exercises, 
 Bronchial hygiene, 
 Health education, 
 Bike exercise for 20 minutes (excluding history of hip operation done) 
 Walking exercise at least 50m or as tolerated 
 Activity of daily living training by Occupational Therapists 
 Dietitian referral if needed, to ensure adequate nutrient intake. 
 
A standardized resistance training (Patterson, 2019)  
 
Exercise: Isotonic knee extension 
 
Sessions per week: 6 (Except Sunday and public holiday) 
 
Duration of intervention: 2 weeks 
 
Total number of sessions during hospitalization: 12 sessions 
 
Sets per session: 4 (Total Repetitions: 75reps in total across 4 sets) 
 
Rest between sets: 30s 
 
Execution speed: 1-2s 
 
Load: 15-30% of 1 repetition maximum(1-RM) (Loenneke, 2012) 

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 
Involvement of limb per session: Alternate limb training on alternate 
day 
 
Execution: until planned rep scheme is completed or contraction 
failure 
 
Remarks: If at any time the patient becomes dizzy, severe discomfort 
(e.g. pain, numbness), training will be stopped. 
 
The BFR-RE intervention group (Patterson, 2019)  
The participants will have the above-mentioned resistance training with 
“BFR-device” with details as follows: 
 
Cuff size: medium 
 
Restriction time: 5- 10 mins (stop after finishing 4 sets of training or 
terminating by Physiotherapists) 
 
Applied location: alternate quadriceps in consecutive day 
 
Applied pressure: 80% limb occlusion pressure (LOP) 
 
Control group 
Same standardized 2-week in-patient rehabilitation and same amount of the 
above-mentioned resistance training without the “BFR device”. 
 
Determination of maximal voluntary isometric contraction (MVIC) (Hul, 
2004) 
 
Maximal voluntary isometric contraction (MVIC) is the simplest way to 
measure the force-producing capabilities of a muscle group 
objectively during its isometric contraction condition which means 
muscle group under contraction with a constant velocity of joint 
motion and muscle length. (The National Isometric Muscle Strength 
(NIMS) Database Consortium, 1996) 
 
Computer dynamometer will be used to measure the MVIC of the 
isometric knee extension of the dominant leg. 
 
Patient will be seated in hip flexion of 90°, knee flexion of 90°, and 
the padded force transducer set around malleolus. The lever arm 
(distance between the force transducer and the point of rotation) will 
be recorded for calculation of force produced by the computer 
dynamometer. 
 
Upper body will be stabilized and verbal encouragement will be given 
to the participants in a standardized way. 
 
3 submaximal warm-up contractions trials will be given with 1-minute 
rest afterwards. 

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 
3 trials of MVIC with 1 min of rest between each trial will be instructed. 
After a build-up phase of 2 s, an MVIC needs to be in a steady, 
maximal contraction, with a plateau phase of 3 s. 
 
During measurements, the Physiotherapists can have visual 
feedback of the force signal, monitoring the quality of the shape of 
each contraction. 
 
The highest value for MVIC will be captured for future analysis. 
 
Determination of 1-repetition maximum (1-RM) (Kanada, 2017; Takeichi, 
2012) 
1RM (kg)=0.188 + 0.187 × maximal isometric muscle strength. This formula 
was devised based on examination of 176 in-patient elderlies in Japan (352 
legs). 
 
Determination of Hand grip strength (HGS) (Jeong, 2017; Yu, 2017) 
 
In sitting position with elbow in 90-degree flexion 
 
Hold dynamometer by the testing hand with the grip meter indicator 
facing outward, and away from any part of the body. 
 
Allow 1 practice trial for dominant hand. 
 
Squeeze the grip with full force and continuously for at least 2 
seconds. 
 
Two trials for handgrip strength test for the dominant hand 
 
Not to swing the grip dynamometer during the test and not to hold 
their breaths. 
 
The time between each trial: ~30s; 
 
The time interval between trials of the same hand: ~1min 
 
Verbal encouragement by Physiotherapists.  
 
HGS will be the average of the reading displayed on the 
dynamometer in the 2 trials 
 
Determination of limb occlusion pressure (LOP) 
 
Limb Occlusion Pressure (LOP) is the minimum pressure required, at 
a specific time in a specific tourniquet cuff applied to a specific 
patient’s limb at a specific location, to stop the flow of arterial blood 
into the limb distal to the cuff. (Noordin, 2009) 
 
The 3rd generation tourniquet system features a built-in LOP 
measurement capability. This allows a personalized tourniquet 
pressure for each individual patient and eliminated the need to 
account for cuff width, limb size or blood pressure. 

Study Protocol_v2_ updated on 8.7.2020 
 
 
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Determination of Leg dominance (Melick, 2017) 
Since mobility is a bilateral mobilizing task, the leg dominance will be defined 
by the participant’s preferred leg to shoot a ball when being asked the following 
question: “If you would shoot a ball on a target, which leg would you use to 
shoot the ball?” 
 
Determination of completeness of training 
80% of the whole course of in-patient additional muscle strength training 
(i.e.10 out of 12 sessions) 
 
Determination of acceptance of program 
5-point Likert scale will be given to participants after the additional muscle 
strength training (i.e. very like, like, no comment, dislike, very dislike) 
 
Data collection timepoint 
 Baseline 
 After completeness of training (i.e. at least 10 sessions of training) 
 
Clinical investigations 
 Laboratory tests at baseline and post training program 
 
Clotting profile, Complete blood count (CBC), liver function test 
(LFT), renal function test (RFT), serum creatinine kinase level 
(CK), serum lactic acid level, C-reactive protein (CRP) 
 
Estimated 32ml of venous blood in total will be needed for both 
pre and post training blood tests.   
 Myoglobulin in urine 
 Spirometry before discharge of current admission 
 
 
 
 
 
 
 
 
 
Primary outcome: 
Localized Muscle Strength (Robles, 2011; Hul ,2004) 

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 
Muscle strength is operationally defined as subject’s capability for the 
exertion of force or torque to an external dynamometer over a specified 
period of time. (Kroemer, 1980)  
 
Maximal voluntary isometric contraction (MVIC) of knee extension of the 
dominant leg, with a unit Newton (N), will be assessed by computer 
dynamometry. 
 
Secondary outcomes: 
 Functional test 
 Short physical performance battery (SPPB) (Mora, 2015) 
Gait speed with 4m distance, Balance test & repeated chair 
stands test 
 6-minute walk test (Holland, 2010) 
 Systemic muscle strength (Jeong, 2017; Yu, 2017) 
 
Hand grip strength, a non-invasive marker of systemic skeletal 
muscle strength and function, is assessed by handheld grip 
dynamometer of dominant hand 
 Health related quality of life 
 
Self-administered Chinese version of COPD assessment test 
(CAT) (Karloh,2016) 
 Acceptability of BFR-RE 
 
Pain by visual analog scale (0-10) before, immediate and 5-min 
post exercise  
 
Participant’s acceptance by a Likert 5-point categorical scale 
after the whole program 
 Feasibility of BFR-RE 
 
Examination of drop-out rate and reasons of drop-out in those 
discontinuing the training 
 Unplanned readmission rate within 1 month of discharge for 
COPDAE 
 
 
 
 
 
 
 
Data analysis 
SPSS version 17.0 will be used for statistical analysis. 

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The comparison of baseline characteristics of subjects across the 2 groups will 
be tested by independent t-test for continuous variables (e.g. age, 
anthropologic data, maximum voluntary isometric contraction of knee 
extension of dominant leg, hand grip strength of dominant hand, laboratory test 
results, spirometry data, 6-minute walk test, COPD Assessment test (CAT), 
etc.), Chi-square test for nominal variables (e.g. presence of myoglobulin in 
urine, etc.). 
For testing between-group and within-group changes after Blood flow 
restriction resistance exercise (BFR-RE), multivariate repeated measures 
ANOVA will be used. 
All continuous variables are presented as mean ± SD (standard deviation). 
The level of statistical significance was set at p < 0.05. 
 
Sample size calculation 
A priori power analysis (calculated by G*Power 3.1.9.5) showed that in order to 
have a power of 80% to detect a difference of medium effect (f squared: 0.22) 
of muscle strength gain (Cook, 2017) at the 0.05 level of significance, 18 
patients is needed in each group. If a dropout rate of 30% is estimated, 48 
patients in total will be needed for the study. 
 
Randomization 
Participants are randomized into one of the two treatment groups. A computer 
compiles randomization list. Based on randomization, envelopes are made 
with participant number, including allocation of patients to BFR-RE vs. without 
BFR-RE. The envelopes are opened after inclusion for the individual 
participant only. The randomization list is kept in a sealed envelope. 
Stratification of participants into two groups by maximum voluntary isometric 
contraction (MVIC) at baseline before randomization will be done. The cutoff 
for the stratification will be determined from the data in the recent service. 
 
Blinding 
Participants, doctors, nurses and involved Physiotherapists are for obvious 
reasons not blinded, but assessments at recruitment and on discharge will be 
carried out by blinded Physiotherapists without knowledge of treatment group. 
 
 
 
Interruption 
The individual participant can withdraw from the study at any time. Participants 

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may also be excluded from the study at any time based on the investigator's 
evaluation. 
 
Data registration 
All data relevant for the study are recorded in a specific form. 
Data of each enrolled participant are listed in a personal form. 
 
Recruitment 
Consecutive patients will be recruited in the three pulmonary wards in Haven 
of Hope Hospital between 10.6.2020 – 28.2.2021. The study will be expected 
to finish within 9 months or earlier if the expected recruitment achieved. 
 
Expected Benefits 
BFR-RE may improve the muscle strength of the knee extension and muscle 
size of quadriceps in the patients undergoing early rehabilitation for COPDAE. 
This may allow patients to actively participate the resistance training to 
improve the mobility function, subsequently health-related quality of life. 
 
Adverse events 
In this context, adverse events are defined as any unintended, unfavorable 
finding, symptom or disease that can be connected to the strength training, 
whether it is deemed to have a correlation with this or not. Adverse events are 
recorded by spontaneous registration as well as by open questioning. 
 
Concerns on patient’s safety 
Delayed onset of muscle soreness (DOMS) 
DOMS is normal after exercise, including after LL-BFR training. It was reported 
in 40% of participants in a survey before but this will subside within 24-72 
hours (Patterson, 2018). 
 
Numbness 
Incidence of transient numbness is between <2% (Nakajima, 2006) to 18.5% 
(Patterson, 2018). This is related to the tourniquet pressure causing peripheral 
nerve compression. 
 
 
 
Central vascular response 
Continuous BFR-RE (keep restriction during rest period between sets) will 

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11 
 
increase the heart rate (HR), systolic blood pressure (SBP), diastolic blood 
pressure (DBP), or double product (HR x SBP) compared with same exercise 
in free flow conditions. 
 
Cardiac output is not affected by BFR during exercise since HR increases and 
stroke volume decreases proportionally compared to non-BFR groups. 
Changes in central hemodynamic response are blunted after BFR-RE when 
compared to HL-RE. However, there was reported to be 14.6% of fainting / 
dizziness related to BFR-RE (Patterson, 2018). The study is not blinded to the 
physical therapists; thus, the identification of any safety issues will be easy. 
 
Venous thromboembolism (VTE) 
The incidence rate of VTE in general population in Asia was 0.2-0.26% 
(Klatsky, 2000). However, there are minimal adverse events related to this 
possible complication reported in BFR-RE literature. Most studies use blood 
markers to assess the risks of VTE BFR-RE. There is no rise in D-dimers, 
prothrombin fragment, thrombin-antithrombin III complex, C-reactive protein 
immediately after BFR-RE training or weeks after training (Madarame, 2013). 
The reported incidence rate of venous thrombus in a large epidemiologic 
questionnaire (Nakajima, 2006) in Japan was 0.055% and pulmonary 
embolism was 0.008%. 
 
Moreover, BFR-RE demonstrated a stimulation of fibrinolytic system by 
increased tissue plasminogen activator (t-PA), a thrombus-degrading protein in 
the epithelial cells in healthy participants (Nakajima, 2007). 
 
Other vascular concerns (Patterson, 2018) 
There are reported superficial thrombophlebitis (0.8%) and subcutaneous 
hemorrhage (0.8%). Bruising was reported to be 13.1% (Nakajima, 2006). 
 
Rhabdomyolysis 
It is a clinical syndrome due to skeletal muscle damage and the release of 
potentially toxic substances into the circulation. The reported risk was between 
0.07-0.2% (Thompson, 2018). The survey (Nakajima, 2006) in Japan revealed 
the low incidence of 0.008%. However, this risk was not extraordinarily higher 
than traditional HL-RE training. 
 
Education 
Observations and measurements are carried out by physiotherapists, 

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occupational therapists, doctors associated with the project. 
 
Serious adverse events 
In this context, serious adverse events are defined as events or reactions that 
cause: 
 
Death 
 
Life-threatening situations 
 
Urgent transferal to acute hospital or prolongation of existing 
hospitalization 
 
Permanent or severe disability/incapacity 
 
Serious adverse events must be evaluated by the investigator for possible 
correlations with treatment in the intervention group, to consider whether there 
is a reasonable possibility that the adverse event has been caused by that. 
The following factors are included in the evaluation: 
 
Consistency of time. 
 
Conformity with known effects of the treatment. 
 
Alternative reasons. 
 
If a serious adverse event is considered to have a causal correlation with the 
treatment, the investigator must consider the study to be terminated ahead of 
time. 
 
Ethics 
The study will be conducted in accordance with the principles of the Helsinki 
Declaration. 
The protocol including patient information and consent forms for the 
randomized study is approved by the Research Ethics Committee. 
The investigator is responsible for informing the Research Ethics Committee of 
any serious adverse event and/or major changes in the protocol. The 
coordinating investigator files all correspondence. 
During the study period, data will be disclosed to the investigator of the study 
only. The research data of subjects will be masked with a set of project codes 
assigned to the subjects. A matching list with subjects' information will be 
kept away from the project files physically and electronically. Data will be well 
covered and stored in a locked room when it is not in used or after the study. 
Electronic data will be encrypted. All study data will be locked in cabinets 
where the department keeps patient/confidential information. Electronic data 
will be saved in secured computer of the hospital with restricted access. The 

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principal investigator will be responsible for its safe keeping. The data will be 
kept for three years and then discarded following the guideline of HA after 
completion of storage period. 
 
~ THE END ~ 
 
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Nakajima, T., Takano, H., Kurano, M., Iida, H., Kubota, N., Yasuda, T., … 
Morita, T. (2007). Effects of KAATSU training on haemostasis in healthy 
subjects. International Journal of KAATSU Training Research, 3(1), 11–20. doi: 
10.3806/ijktr.3.11 
 
Noordin, S., Mcewen, J. A., Kragh, C. J. F., Eisen, A., & Masri, B. A. (2009). 
Surgical Tourniquets in Orthopaedics. The Journal of Bone and Joint 
Surgery-American Volume, 91(12), 2958–2967. doi: 10.2106/jbjs.i.00634 
 
Patterson, S. D., & Brandner, C. R. (2018). The role of blood flow restriction 
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Patterson, S. D., Hughes, L. R., Warmington, S. L., Burr, J. A., Scott, B. R., 
Owens, J. undefined, … Loenneke, J. undefined. (2019). Blood Flow 
Restriction Exercise: Considerations of Methodology, Application, and 
Safety. Frontiers in Physiology, 10(533), 1–15. doi: 10.3389/fphys.2019.00533  
 
Robles, P. G., Mathur, S., Janaudis-Fereira, T., Dolmage, T. E., Goldstein, R. 
S., & Brooks, D. (2011). Measurement of Peripheral Muscle Strength in 
Individuals with Chronic Obstructive Pulmonary Disease. Journal of 
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Swallow, E. B., Reyes, D., Hopkinson, N. S., Man, W. D.-C., Porcher, R., Cetti, 
E. J., … Polkey, M. I. (2007). Quadriceps strength predicts mortality in 

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patients with moderate to severe chronic obstructive pulmonary disease. 
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& Matsunaga, Y. (2012). Prediction of 1 repetition maximum strength from 
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~END~ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Department of Medicine, Haven of Hope Hospital 
Subject Informed Consent Form 
 
Project Title 
Effects on muscle strength after blood flow restriction resistance exercise (BFR-RE) in early 
in-patient rehabilitation of chronic obstructive pulmonary disease acute exacerbation 
(COPDAE), a single blinded, randomized controlled study 
 
Introduction 
You are invited to participate in the randomized controlled trial of the blood flow restriction 
resistance training (BFR-RE) in early rehabilitation of chronic obstructive pulmonary disease 
acute exacerbation (COPDAE) in the Haven of Hope Hospital. 
 
BFR-RE was invented by Dr. Yoshiaki Sato in Japan 40 years ago. This exercise makes use 
of a pneumatic band to reduce the blood flow of the distal limb. This can accumulate the 
metabolites generated during exercise in order to promote muscle growth and increase muscle 
strength.  
 
BFR-RE is newly introduced to Physiotherapy Department of Haven of Hope Hospital in 
March, 2020 though it is not a common practice in Hospital Authority. However, the 
“BFR-device” is in its 3rd generation currently with tremendous research showing promising 
results. Under the guidance of a certified physiotherapist, a “low load intensity” can be used 
for resistance training to build up muscle mass and strength by applying the device over the 
thigh to partially limit the blood flow to the distal limb. 
 
BFR-RE is well studied in athletes, elderlies and patients for rehabilitation after orthopaedics 
surgeries. A large amount of literature reveals BFR-RE with “low load intensity” shows 
comparable increase of muscle mass as “high load intensity” resistance training and more 
increase of muscle strength than those only undergoing “low load intensity” resistance 
training. 
 
The objective of this study is to investigate the additional effects of 2-week BFR-RE in 
patients with COPDAE on top of the conventional in-patient rehabilitation training. 
 
 
 
 
Participant Reference No.: 
____________________ 

Study Protocol_v2_ updated on 8.7.2020 
 
 
19 
 
 
Study Participants 
48 in-patients with COPDAE will be recruited in order to find out the effect of BFR-RE. They 
will be randomly allocated into two groups by drawing enclosed envelope containing the 
assigned groups. One is BFR-RE, the other is control group for comparison. All the patients 
will be medically screened by doctors in the Department of Medicine, Haven of Hope 
Hospital (HHH) before participating in this study. 
 
Assessment procedures 
Both group of participants will undergo the following baseline and post training assessments: 
1. To test the muscle strength of knee extension by computer dynamometer 
2. ‘Short physical performance battery’ (SPPB) under the instruction of physiotherapists. 
 
Balance study, 4m gait speed assessment, 5 times sit-to-stand test 
3. 6-minute walking test (6 MWT) 
4. Hand grip strength by hand grip dynamometer 
5. A self-administered Chinese version of COPD assessment test (CAT) 
6. Discomfort assessment before and post training 
7. Blood and urine specimens will be collected to investigate the metabolic change with this 
exercise.  
 
Pre-exercise blood taking will be done in the same setting with other routine 
admission blood specimen collection ensuring no additional needle pricking 
 
Post-exercise blood taking will be taken place after finished the whole course. 
 
The estimated amount of blood will be 32ml in total of pre and post exercise 
tests. 
The estimated time required to complete the questionnaire and assessment is 1 hour. 
 
Standard Treatment 
Standardized 2-week in-patient rehabilitation consists of 
 Breathing exercises, 
 Bronchial hygiene, 
 Health education, 
 Bike exercise for 20 minutes (excluding history of hip operation done) 
 Walking exercise at least 50m or as tolerated 
 Activity of daily living training by Occupational Therapists 
 Dietitian referral if needed, to ensure adequate nutrient intake 
 
Standardized Muscle Strength Training  
 Exercise: knee extension 

Study Protocol_v2_ updated on 8.7.2020 
 
 
20 
 
 Sessions per week: 6 (Except Sunday and public holiday) 
 Duration of intervention: 2 weeks 
 Total number of sessions during hospitalization: 12 sessions 
 Sets per session: 4  (Total Repetitions: 75 reps in total across 4 sets) 
 Rest between sets: 30 seconds 
 Execution speed: 1-2 seconds 
 Load: 15-30% of 1 repetition maximum(1-RM) (Loenneke, 2012) 
 Involvement of limb per session: Alternate limb training on alternate day 
 Execution: until planned rep scheme is completed or contraction failure 
 Maximum time for training: 8 minutes (preset safety time limit for the BFR device) 
 Remarks: If at any time the patient becomes dizzy, severe discomfort (e.g. pain, 
numbness), training will be stopped. 
 
BFR-RE intervention group  
The patient will have the above-mentioned muscle strength training with “BFR-device” with 
details as follows: 
 Cuff size: medium 
 Restriction time: 8 mins (stop after finishing 4 sets of training or terminating by 
Physiotherapists or maximum restriction safety time limit preset by the BFR device) 
 Applied location: alternate quadriceps in consecutive day 
 
Applied pressure: 80% limb occlusion pressure (LOP). 
 
All the instructors of the exercise are certified Physiotherapists who have attended the 
official training session of the device.  
 
Control group 
Same standardized 2-week in-patient rehabilitation and same amount of above-mentioned 
muscle strength training without the “BFR device” 
 
If the participant is allocated to the control group, the one will not receive BFR-RE afterwards 
since a prolonged hospitalization may be required to complete another 2-week course of 
training.  
 
Alternative Procedures or Treatments 
If the participant decides not to join this study, the one will proceed to undergo the routine 
in-patient rehabilitation as usual since the current standardized muscle strength training is a 
usual practice without the BFR device. All follow-ups and examinations subsequently will be 
conducted in the same manner whether you opt to join the study or not. 
 

Study Protocol_v2_ updated on 8.7.2020 
 
 
21 
 
Expected Benefits 
BFR-RE may improve the muscle strength of the knee extension and muscle size of 
quadriceps in the patients undergoing early rehabilitation for COPDAE. This may allow 
patients to actively participate the resistance training to improve the mobility function, 
subsequently health quality of life. 
 
Foreseeable Risks or Discomforts 
 Delayed onset of muscle soreness (DOMS) which will subside within 24-72 hours (40%) 
 
Numbness which is transient (2% - 18.5%) 
 
Dizziness (<15%) 
 
Bruising (<15%) 
 
Superficial thrombophlebitis (<1%) 
 
Subcutaneous hemorrhage (<1%) 
 
Rhabdomyolysis (<0.3%) 
 
Deep vein thrombosis (<0.06%) 
 
Pulmonary embolism (<0.01%) 
 
Expected Duration of Research   Within 3 weeks 
 
Study Termination 
Your participation in this study can be terminated when you withdraw from the study at any 
time or you cannot adhere to the protocol. If the participant attends less than 80% of the 
training sessions (i.e. less than 10 out of 12 sessions), the one will be counted as a drop out 
group.  
 
Cost and Payment of the Study 
Apart from paying standard hospital fees, you are not required to pay additional fees and will 
not receive any remuneration. 
 
New Information  
You will be informed if any new information about this study becomes available that may 
affect your decision to continue participation in the study. 
 
Compensation and treatment for study related injury 
If the result of your participation in this study caused any physical injury, the investigator will 
treat you or refer you for treatment. You are not giving up any of your legal rights by signing 
this form. 
 

Study Protocol_v2_ updated on 8.7.2020 
 
 
22 
 
Voluntary participation/ Withdrawal  
Participation in the study is voluntary. Your decision to participate or not will be respected.  
You have the right to terminate your participation at any time and without giving any reason 
during the study, and this will not affect your present or future medical care. If you feel 
uncomfortable in any way during the session, you may not continue to participate in the study. 
If you withdraw from the study, the data collected up to your withdrawal will not be used 
unless with your consent. You may also express your consent to research team through 
Subject Informed Consent Form to allow research team to continuously use data collected 
before your withdrawal for research purpose. You can take time to decide whether or not you 
wish to take part. By signing a written consent form, you will be given a study information 
sheet and a signed informed consent form for record. 
 
Confidentiality 
Your confidentiality will be the highest priority. If the information you provide is reported or 
published, this will be done in a way that does not identify you as its source.  To ensure the 
highest form of confidentiality, we do not fill in your name on the questionnaire.  Your 
signed consent form will be stored separately from your personal data to further protect your 
confidentiality. Access to the data will be restricted to the researchers of this study. Along 
with this, the research documents as well as personal data will be stored in the computers 
which are only accessible by the researchers. Data can be withdrawn and destroyed if 
requested by you and all data will be destroyed three years after the completion of the study. 
 
Under the laws of Hong Kong (in particular the Personal Data (Privacy) Ordinance, Cap 486), 
you enjoy or may enjoy rights for the protection of the confidentiality of your personal data, 
such as those regarding the collection, custody, retention, management, control, use 
(including analysis or comparison), transfer in or out of Hong Kong, non-disclosure, erasure 
and/or in any way dealing with or disposing of any of your personal data in or for this study. 
For any query, you should consult the Privacy Commissioner for Personal Data or his officer 
(Tel no.: 2827 2827) as to the proper monitoring or supervision of your personal data 
protection so that your full awareness and understanding of the significance of compliance 
with the law governing privacy data is assured. 
 
By signing a written consent form, you are authorizing the Research Ethics Committee (REC) 
and the regulatory authority(ies) will be granted direct access to your study data for data 
verification. 
 
Enquiry 
If you have any questions related to this project can be addressed to the principal investigator 

Study Protocol_v2_ updated on 8.7.2020 
 
 
23 
 
Dr. LAU Chung Wai, Resident, Department of Medicine, Haven of Hope Hospital at 2703 
8888. 
 
If you have questions related to your rights as a research participant, please contact Research 
Ethics Committee (Kowloon Central / Kowloon East) at 3506 8888. 

Study Protocol_v2_ updated on 8.7.2020 
 
 
24 
 
Project Title 
Effects on muscle strength after blood flow restriction resistance exercise (BFR-RE) in early 
in-patient rehabilitation of chronic obstructive pulmonary disease acute exacerbation 
(COPDAE), a single blinded, randomized controlled study 
 
I (full name) _______________________ agree to participate in the randomized controlled 
trial of the blood flow restriction resistance training (BFR-RE) in early rehabilitation of 
chronic obstructive pulmonary disease acute exacerbation (COPDAE) in the Haven of Hope 
Hospital. 
 
The purpose of this research is to investigate the additional effects of a 2-week BFR-RE in 
patients with CODPAE on top of conventional in-patient rehabilitation training. 
 
I understand that participation in this project will involve me participating a 2-week of 
standardized muscle strength training with or without “BFR-device” according to study 
protocol in the Haven of Hope Hospital on top of the conventional in-patient rehabilitation 
training and taking part in the outcome assessment before and after the additional training. 
 
I further understand that any information obtained in this study will remain very strictly 
confidential and will be used for research purposes only. 
 
My participation is voluntary. I am free to withdraw from this study at any time with no 
adverse consequences. 
 
If I request to withdraw from this study, I  agree /  disagree my research data provided 
before my withdrawal will be continuously used by the investigator. 
 
I understand that my identity will be kept confidential. I agree to authorize the Research 
Ethics Committee (REC) and the regulatory authority(ies) a direct access to my research data 
for verification of clinical trial data, without violating my confidentiality, to the extent 
permitted by the applicable laws and regulations. 
 
 
 
 
_____________________    
______________________  
______________ 
Name of Participant  
     Signature of Participant     
 
 Date 
(Block Letters) 

Study Protocol_v2_ updated on 8.7.2020 
 
 
25 
 
 
 
 
 
_____________________ 
     _________________________  
______________ 
Name of Impartial Witness  
 Signature of Impartial Witness           Date 
If Applicable (Block Letters) 
An impartial witness’s signature should be included if the participant is unable to read or 
write. 
 
 
 
_____________________ 
    _________________________ 
 
______________ 
Name of Investigator  
 
  Signature of Investigator 
 
         Date 
(Block Letters)  
 
I will be given a signed copy of subject informed consent form for reference.