Table 2: CONSORT 2010 checklist

Section/Topic Ite Standard Pag

m Checklist item e No
No *

Title and abstract

1a Identification as Efficacy and safety evaluation of intravenous

a randomised infusion of cervusand cucumis polypeptdes for
trial in the title treatment of avascular necrosis of the femoral
head:a randomized clinical trial

1b Structured OBJECTIVE: To investigate the efficacy and safety

summary of of intravenous cervus and cucumis polypeptides
trial design, for treating avascular necrosis of the femoral head
methods, (ANFH) in regard to pain and hip function in a ran-
results, and domizedclinicaltrial.
conclusions (for
specific METHODS: A total of 96 subjects with ANFH who
guidance see were recruited at the Orthopaedic Hospital Affiliat-
CONSORT for ed with Hebei United University and Qian Hai Fem-
abstracts)1,2 oral Head Hospital of Beijing were assigned by lot-
tery to an intervention group (n = 48) or a control
group (n = 48). All subjects underwent physical
therapy and rehabilitation exercises. In addition,
subjectsintheinterventiongroupweregivenintra-

venous infusions of cervus and cucumis polypep-

tides. Visual analogue scale (VAS), Harris hip score,
and radiography or magnetic resonance imaging
were applied to assess all subjects at the beginning
of treatment and 3, 6, and 9 months afterward. All
thesubjectswerefollowedupfor2years.

RESULTS: At the beginning of treatment, there

were no statistically significant differences be-
tween the two groups in terms of the general con-
dition of patients or the VAS and Harris hip scores
(all P > 0.05). At 3, 6, and 9 months after
treatment, however, the VAS score decreased and
the Harris hip score increased in all patients, with
the im- provement of intervention group
significantly greater than that of the control group
(P < 0.05). The total effectiveness rates for the
intervention and control groups were 89.58% and
70.83%, re-
spectively,withthedifferencebeingstatisticallysig-
nificant (P < 0.05). There was no statistically signifi-
cant difference between the two groups in terms
of thesafetyoftheinjections(P>0,05)

Introduction
Background and 2a Scientific With advances in modern medical technology, an
objectives background and in- creasing number of patients with avascular
explanation of necrosis of femoral head (ANFH) are being
rationale diagnosed.1,2 In the past, there was no effective
treatment for those who de- veloped ANFH, and
they were vulnerable to disability.

2b Specific Some experiments have shown, however, that a

objectives or variety of Chinese drugs had a therapeutic effect
hypotheses on ANFH.5-7 The use of cervus and cucumis
polypeptides has been suggested as a non- invasive
treatment of ANFH and has been reported to
obtainatherapeuticeffect.

Methods

Trial design 3a Description of All subjects were recruited at the Department of

trial design Orthopedic of the Orthopaedic Hospi- tal Affiliated
(such as with Hebei United University and Qian Hai Femoral
parallel, Head Hospital of Beijing. There were 65 men and
factorial) 31 women, with an average age of (41.8 14.0)
including years (range 18-72 years). Duration of ANFH
allocation ratio ranged from 2 months to 12 years [average (2.8
3.2)years]. There were 32 unilateral cases and 64
bilateral cases. The causes of ANFH included
alcoholism in 28 cases, steroid use in 30 cases,
trauma in 15 cases, and other causes in 23 cases.

3b Important A total of 96 subjects were randomly allocated, by

changes to lot- tery, to an intervention group or a control
methods after group, with a 11 allocation ratio.
trial
commencemen
t (such as
eligibility
criteria), with
reasons

Participants 4a Eligibility According to plain radiography, computed

criteria for tomogra- phy, magnetic resonance imaging (MRI),
participants radionuclide bone scans and other tests, all
subjects had a confirmed diagnosis of ANFH. The
diagnostic criteria of ANFH
wereinlinewiththoseintherelevantliterature.

4b Settings and All subjects were attending the Department of

locations where Ortho- pedic of the Orthopaedic Hospital Affiliated
the data were with He- bei United University and Qian Hai
collected Femoral Head Hospital of Beijing between June
2009 and June2010.

Interventions 5 The Thesubjectsintheinterventiongroupweregiven24m

interventions g cervus and cucumis polypeptide (Harbin Gloria
 for each group Phar- maceuticals Co., Ltd., Heilongjiang, China)
with sufficient dissolved in 250 mL 5% dextrose injection (or 0.9%
details to allow sodium chloride) via intravenous infusion once a
replication, day for 15 days as the course of treatment. The
including how intervention group also underwent the same
and when they regimen as the control group, which consisted of
were actually extracorporeal shock wave therapy and
administered rehabilitation exercises.

Outcomes 6a Completely The standard of the effect of treatment was that

defined pre- de- scribed in the relevant literature.3 It included
specified its effec- tiveness for alleviating pain and
primary and improving joint func- tion whether these two
secondary parameters had achieved nor- mal levels or how
outcome close they were to full recovery. Radi- ography
measures, showed that the bone density was even, cystic
including how necrosis was reduced or at least no worse,
and when they trabecular bone had been reproduced, and joint
were assessed space was nor- mal.

6b Any changes to All subjects were evaluated by the Harris hip score,
trial outcomes which including assessments of pain, function,
after the trial defor- mity, and motion, as described in the
commenced, literature.10 The degree of hip pain was also
with reasons evaluated by a visual ana- logue scale (VAS) score
(quantifying the number of points on the VAS
scale: e.g., a 5-point VAS scale).The VAS and Harris
scores were recorded respectively, and plain
radiography or MRI was undertaken at the begin-
ningoftreatmentand3,6, and9monthsafterward.

Sample size 7a How sample All subjects were evaluated by the Harris hip score,
size was which including assessments of pain, function,
determined defor- mity, and motion, as described in the
literature.10 The degree of hip pain was also
evaluated by a visual ana- logue scale (VAS) score
(quantifying the number of points on the VAS
scale: e.g., a 5-point VAS scale).The VAS and Harris
scores were recorded respectively, and plain
radiography or MRI was undertaken at the begin-
ningoftreatmentand3,6, and9monthsafterward.

7b When ResearchCir- culation Osseous (ARCO) staging

applicable, criteria were used.9 There were no statistically
explanation of significant differences in terms of age, sex, disease
any interim duration, ARCO stage, causes, location (left or
analyses and right, single or double), or oth-
stopping erdifferencesbetweenthegroups(allP>0.05).
guidelines

Randomisation:
Sequence 8a Method used to A total of 96 subjects were randomly allocated, by
generation generate the lot- tery, to an intervention group or a control
random group, with a 11 allocation ratio. All subjects were
allocation recruited at the Department of Orthopedic of the
sequence Orthopaedic Hospi- tal Affiliated with Hebei United
University and Qian Hai Femoral Head Hospital of
Beijing.

8b Type of There were 65 men and 31 women, with an

randomisation; average age of (41.8 14.0) years (range 18-72
details of any years). Duration of ANFH ranged from 2 months to
restriction (such 12 years [average (2.8 3.2)years]. There were 32
as blocking and unilateral cases and 64 bilateral cases. The causes
block size) of ANFH included alcoholism in 28 cases, steroid
use in 30 cases, trauma in 15 cases, and other
causes in 23 cases. No one in either group
droppedoutorwasexcluded.AssociationResearchCir
- culation Osseous (ARCO) staging criteria were
used.

Allocation 9 Mechanism A total of 96 subjects were randomly allocated, by

concealment used to lot- tery, to an intervention group or a control
mechanism implement the group, with a 11 allocation ratio.
random
allocation
sequence (such
as sequentially
numbered
containers),
describing any
steps taken to
conceal the
sequence until
interventions
were assigned

Implementatio 10 Who generated A total of 96 subjects were randomly allocated, by

n the random lot- tery, to an intervention group or a control
allocation group.
sequence, who
enrolled
participants,
and who
assigned
participants to
interventions
Blinding 11a If done, who An independent researcher who was not informed
was blinded of the treatment sequence or the patient had
after received treatment prior to each out come
assignment to measure mentassessed.
interventions
(for example,
participants,
care providers,
those assessing
outcomes) and
how

11b If relevant, An independent researcher who was not informed

description of of the treatment sequence or the patient had
the similarity of received treatment prior to each out come
interventions measure mentassessed.

Statistical 12a Statistical Statistical software SPSS 17.0 (SPSS Inc., Chicago,
methods methods used IL, USA) was used to analyze data. Measurement
to compare data are presented as mean standard deviation (
groups for x s).
primary and
secondary
outcomes

12b Methods for Stu- dent's t-test was applied to the two groups,
additional and the F test of variance was used for multiple
analyses, such groups. The 2 test was used to analyze
as subgroup numeration data. The Mann-Whitney test was
analyses and used for nonparametric vari- ables. P < 0.05 was
adjusted regarded as denoting statistical sig- nificance
analyses

Results

Participant flow 13a For each group, The subjects were divided into the intervention
(a diagram is the numbers of group (48 cases) and the control group (48 cases)
strongly participants by lottery. None of the subjects of the subjects in
recommended) who were either group dropped out or were excluded. The
randomly study design is de- pictedinFigure1.
assigned,
received
intended
treatment, and
were analysed
for the primary
outcome

13b For each group, There was no statistically significant difference (P >
losses and 0.05) between the two groups in terms of age, sex,
exclusions after disease duration, ARCO stage, causes, location (left
 randomisation, or right, single or double), or other parameters (Ta-
together with ble1).
reasons

Recruitment 14a Dates defining All subjects were attending the Department of
the periods of Ortho- pedic of the Orthopaedic Hospital Affiliated
recruitment with He- bei United University and Qian Hai
and follow-up Femoral Head
HospitalofBeijingbetweenJune2009andJune2010.

14b Why the trial Subjects with necrosis of the femoral head caused
ended or was by factors such as tuberculosis, infection, or a
stopped tumor were excluded from the study. Also
excluded were subjects who had other co-
morbidities, including diabetes, high blood
pressure ( > 140/90 mm Hg), depression, hyper-
thyroidism, pregnancy, severe liver or other organ
dys- function, coagulation abnormalities,
implanted cardiac pacemakers, and acquired
immune deficiency virus in- fection.

Baseline data 15 A table showing According to plain radiography, computed

baseline tomogra- phy, magnetic resonance imaging (MRI),
demographic radionuclide bone scans and other tests, all
and clinical subjects had a confirmed diagnosis of ANFH. The
characteristics diagnostic criteria of ANFH
for each group wereinlinewiththoseintherelevantliterature.8

Numbers 16 For each group,

analysed number of
participants
(denominator)
included in each
analysis and
whether the
analysis was by
original
assigned groups

Outcomes and 17a For each Figure 1 and figure 2

estimation primary and
secondary
outcome,
results for each
group, and the
estimated
effect size and
its precision
(such as 95%
confidence
interval)
 17b For binary The total effectiveness rates (effective and
outcomes, markedly ef- fective) for the intervention and
presentation of control groups were 89.58% and 70.83%,
both absolute respectively. The Mann-Whitney U-test was used
and relative to compare the efficacy of the two groups, and the
effect sizes is difference was statistically significant (Z = 2.403, P
recommended < 0.05).

Ancillary 18 Results of any The standard of the effect of treatment was that
analyses other analyses de- scribed in the relevant literature.3 It included
performed, its effec- tiveness for alleviating pain and
including improving joint func- tion whether these two
subgroup parameters had achieved nor- mal levels or how
analyses and close they were to full recovery. Radi- ography
adjusted showed that the bone density was even, cystic
analyses, necrosis was reduced or at least no worse,
distinguishing trabecular bone had been reproduced, and joint
pre-specified space was nor- mal. Marked effects included
from clinical symptom relief, improved joint function,
exploratory and that the cystic necrosis was under control.
Ineffectiveness of the treatment in- cluded no
significant alleviation of clinical symptoms, no
improvement of joint function, and cystic necrosis
that appeared aggravated or that resulted in
femoral collapse.

Harms 19 All important The subjects were divided into the intervention
harms or group (48 cases) and the control group (48 cases)
unintended by lottery. None of the subjects of the subjects in
effects in each either group dropped out or were excluded. The
group (for study design is de- pictedinFigure1. There was no
specific statistically significant difference (P > 0.05)
guidance see between the two groups in terms of age, sex,
CONSORT for disease duration, ARCO stage, causes, location (left
harms3) or right, single or double), or other parameters (Ta-
ble1).

Discussion

Limitations 20 Trial limitations,

addressing
sources of
potential bias,
imprecision,
and, if relevant,
multiplicity of
analyses

Generalisability 21 Generalisability For young, active patients, however, there are

(external many complications with THA, including thigh pain,
validity, polyethylene wear, osteolysis, and compo- nent
applicability) of loosening.18 Therefore, treatment of THA in the
the trial
 findings youngremainscontroversial.

Interpretation 22 Interpretation In this study, patients in the intervention group

consistent with were given intravenous infusions of cervus and
results, cucumis polypeptides. At 3, 6, and 9 months after
balancing treatment, there were statistically significant
benefits and differences between the two groups in terms of
harms, and the Harris hip and VAS scores (P < 0.05). The total
considering effectiveness rate in the in- tervention group was
other relevant 89.58%, confirming that intrave- nous cervus and
evidence cucumis polypeptides have a positive effect on
ANFH, consistent with the findings of other
studies.

Other information

Registration 23 Registration -
number and
name of trial
registry

Protocol 24 Where the full OnlineSubmissions:http://www.journaltcm.com

trial protocol JTraditChinMed2016February15;36(1):39-44
can be info@journaltcm.com
accessed, if
available

Funding 25 Sources of Department of Orthopae- dics, Orthopaedic

funding and Hospital Affiliated with Hebei United Uni- versity
other support (The Second Hospital of Tangshan), Tangshan
(such as supply 063000,China
of drugs), role
of funders