This study is a prospective, outcome assessor- and data analyst-blinded, randomized controlled design study that compared an ERAS care pathway cohort with standardized care pathway cohort. Emergency admissions with a primary diagnosis of ITF between January 2020 and July 2021 in our hospital will be selectively enrolled. All patients will receive their operation at our hospital where elective surgeries take place predominantly, and they will be treated with PFNA intramedullary fixation at our institution.
The objective of this proposed study is to investigate whether ERAS care pathway will lead to perioperative improvement in ITF patients undergoing intramedullary fixation. The principal investigator (PI) is responsible for the overall project and organizing Steering Committee meetings. PIs of sub-center departments are responsible for gathering experts to carry out the project. An independent Steering Committee will be responsible for affairs such as participants’ safety, meetings, recruitment and follow-up of participants, and quality control. The coordinating center is responsible for communicating protocol modifications and providing materials. This trial includes a 2-week treatment period and a 3-month follow-up period. Outcome assessments will be conducted at baseline, as well as at 3, 14, 30 and 90 days. (Figure 1)
Participants who meet the criteria below are eligible:15
- The patients are over 75 years old.
- X-ray or CT indicate unstable ITF.
- Treated with PFNA intramedullary fixation
- Being willing to undergo surgery with the ERAS pathway.
- Being willing to give informed consent
The exclusion criteria are as follows:15
- Patients are with open fractures or pathological fracture caused by tumor, infection or tuberculosis.
- Patients are with congenital hip dysplasia or osteonecrosis of the femoral head.
- Hip surgery before enrollment.
- Failure to understand or sign informed consent.
Patient population and recruitment procedure
Participants will be recruited from Longhua Hospital affiliated with the Shanghai University of Traditional Chinese Medicine. Prospective participants will be interviewed by the coordinators and informed of the eligibility criteria and the procedure. Those who are eligible and willing to participate the study will be screened initially by baseline assessment and then diagnosed based upon clinical manifestations, physical examination and imaging. Participants will be informed that participating the trial was absolutely voluntary and withdrawal from the trial can be made at any time. In case of withdrawal, the data collected will not be deleted and will be used in the final analyses. A data compilation form including all variables of interest and all potential risks will be completed by the corresponding research center. The information obtained will be stored in an electronic database for subsequent statistical analysis. Recruitment will start in January 2020, and is expected to end in July 2021. The final follow up of all participants will be completed on 30 Sept 2021. The overview of the participant processing and the schedule of evaluation is provided in Figure 1.
Patient and public involvement
Patients and/or public will not involved in the study design and study enrolment
This study is to be conducted in accordance with the principles of the Declaration of Helsinki and has been approved by Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine (TCM).16 The trials have been approved by the appropriate Institutional Review Boards. The clinical trial has been approved by the Institutional Review Board of Longhua Hospital, Shanghai University of TCM. All participants will be given sufficient time to reach a decision to sign the consent form prior to the study in compliance with Good Clinical Practice Guidelines that guides the appropriate use of TCM in clinical practice. Then the participants will be randomized into two groups of different treatments. Reporting will be guided by the CONSORT statement.17,18
ERAS care pathway
An evidence-based process using the best available literature and Delphi expert-opinion method was used to establish the ERAS pathway integrated Chinese and western medicine. The basic components of the multi-disciplinary ERAS pathway which we used are shown in Table 1. The principles include educational program, management of nutrition, management of dietary, management of sleep, management of pain selection of anesthesia, control of bleeding, management of body temperature, prevention of infection, management of anesthesia, management of rehydration management of drainage tube, control of nausea and vomiting, management of activity.
Traditional care pathway
There was no detailed plan in the controlled group, anti-infection, anti-coagulation and other measures were taken to prevent complications during the perioperative period.
Randomization and Allocation
After the screening, patients will be randomized into two groups with an allocation ratio of 1:1. The randomization will be generated via SAS PROC PLAN software (SAS Inc., Cary, NC, USA) by an independent 3rd-party clinical research organization (Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science) and concealed from the researchers by a senior data manager who is not involved in the study. The group assignment list will be sealed in opaque envelopes and be opened by the researchers following informed consent procedures and baseline testing.
All the investigators, physicians, nurses, assessors, analysts, and participants will be blinded to the group assignment until the end of the trial, when all statistical analyses are finished. If, after the first administration, any adverse event potentially related to the treatment occurs, the study physician will re-evaluate the participant, and PI will decide whether the non-blinded procedure is necessary. If non-blinding is required, the allocation information will be provided.
Primary outcome measurements
LOS (length of stay) associated with ITF is a major public health issue due to the aging population and it is the most objective outcome of evaluating the recovery pathway. Furthermore, high LOS would correspond with increases in postoperative complications.14,19 So we chooses the LOS at discharge as the primary outcome measurement to assess the speed of recovery. Economic indicators including major medical expenses, bed expenses, drug expenses, inspection expenses, operation expenses, cost of anesthesia, nursing care and blood transfusion are the other primary outcome measurement.
Secondary outcome measurements
Postoperative joint specific function will be measured using the Harris score, which is widely used to assess the joint function of life for ITF patients. The Harris score is composed of 10 questions, 2 questions (ROM and absence of deformity) for the physician physical examination component and 8 questions for the patient-reported outcome component.20-24 VAS is a reliable and valid measurement of pain. It has a horizontal, 100-mm-long line, with “no pain” recorded on the left side (score: 0) and “pain as bad as it could be” on the right side (score: 10).25 The other secondary outcomes included time to get out of bed, 30 day readmission rates, postoperative transfusion rates, discharge to home and mortality.
Infection, deep venous thrombosis, cardiovascular accidents will be recorded at each visit during treatment.
Sample size calculation
We calculate the sample size according to our primary study. We conducted a preliminary clinical trial and pilot trial about ERAS care pathway versus traditional care pathway from January 2018 to May 2018. The primary outcome parameter was the LOS. Based on the previous results, we found that primary outcome parameter of ERAS care pathway group was 5.8 days, and that of the traditional care pathway group was 9.2 days. According to the formula of the rate in completely random design, n1=n2= , among which, n1 and n2 were the number of patients in the two respectively, =1.96 when type 1 error is 0.05, =1.282 when type II error is 0.1 in two-sided tests. is the mean of and .26 A two-sided 5% significance level and 90% power in detecting treatment differences were considered, and the above relevant data were input into SPSS 20.0 software. This number of patients actually provided less than 80% power, considering an estimated dropout rate of 20%. Therefore, we will recruit a total of 72 patients with 36 patients in each group.
Prior to all analyses, a detailed statistical analysis protocol will be developed. All data will be analyzed in the clinical research center of Longhua Hospital affiliated to Shanghai University of TCM by statisticians blinded to allocation using the SPSS 20.0 statistical software (SPSS Inc., Chicago, Illinois). Efficacy and safety analyses will be conducted according to the intention-to-treat principle using the “last observation carried forward” rule. Before randomization, baseline characteristics will be collected as descriptive statistics for each patient, including gender, age, BMI, duration of symptoms, preoperative red blood cell count and preoperative hemoglobin count. The data analysis of the primary outcome is based on the per-protocol population as a supportive analysis. Mean, standard deviation, median, quartiles and inter quartiles for continuous variables, and frequency for categorical variables will be calculated. Continuous variable followed the normal distribution will be presented as means with standard deviations (SDs) and calculated by an independent sample Student’s t-test, otherwise the data will be expressed as medians with ranges, and non-parametric tests will be used. Categorical variables will be expressed as number (%) and analyzed by χ2 test or Fisher’s exact test. A P value of less than 0.05 is defined as statistical significant with 2-sided 90% confidence intervals (CIs). Missing data will be input with the last observed response carried forward for all measures using the “last-value-carried-forward” principle.
Prior to the clinical trial, we will carry out unified training to make sure all the physicians, nurses, and assessors involved fully understand the process of the trial, including selecting patient screening and selection, case report form writing and manipulation details. To guarantee the quality of the whole trial, rigorous monitoring will be performed by 3 trained quality supervisors. During the trial, supervisors will check on case report forms and intervention twice a month. After verifying the case report forms, data will be input into the database by two full-time research members independently. The standard operating procedures (SOP) will be invariably followed. Drop-outs, withdrawals (and the reasons) and any compliance of all patients occurring will be recorded in detail by the inspectors throughout the treatment and follow-up period.