Keywords
Avascular Necrosis, Femoral Head, Core Decompression, Bisphosphonate Therapy, Randomized Control Trial, Harris Hip Score, Radiographic Changes, Clinical Outcomes, Skeletal Maturity, Orthopedics.
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Lohiya A and Dhaniwala N. Randomised control trial on management of early avascular necrosis of femoral head by core decompression with bisphosphonate therapy versus core decompression in tertiary care hospital in central India [version 1; peer review: 1 approved with reservations]. F1000Research 2024, 13:398 (https://doi.org/10.12688/f1000research.146853.1)
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Study Protocol
Randomised control trial on management of early avascular necrosis of femoral head by core decompression with bisphosphonate therapy versus core decompression in tertiary care hospital in central India
[version 1; peer review: 1 approved with reservations]
PUBLISHED 26 Apr 2024
OPEN PEER REVIEW
REVIEWER STATUS
This article is included in the Datta Meghe Institute of Higher Education and Research collection.
Abstract
Corresponding author:
Ashutosh Lohiya
Competing interests:
No competing interests were disclosed.
Grant information:
The author(s) declared that no grants were involved in supporting this work.
Copyright:
© 2024 Lohiya A and Dhaniwala N.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Lohiya A and Dhaniwala N. Randomised control trial on management of early avascular necrosis of femoral head by core decompression with bisphosphonate therapy versus core decompression in tertiary care hospital in central India [version 1; peer review: 1 approved with reservations]. F1000Research 2024, 13:398 (https://doi.org/10.12688/f1000research.146853.1)
First published: 26 Apr 2024, 13:398 (https://doi.org/10.12688/f1000research.146853.1)
Latest published: 26 Apr 2024, 13:398 (https://doi.org/10.12688/f1000research.146853.1)
Introduction
Avascular Necrosis of the femoral head (AVNFH) is a debilitating condition characterised by the disruption of blood supply to the femoral head, leading to ischemic necrosis and subsequent structural damage. It commonly affects individuals in the prime of their lives, resulting in pain, functional impairment, and, if left untreated, progression to hip joint degeneration. The aetiology of AVNFH is diverse, encompassing traumatic injuries, corticosteroid use, and systemic diseases such as sickle cell anaemia and systemic lupus erythematosus.1
Core decompression has emerged as a promising surgical intervention for early-stage AVNFH, aiming to alleviate pain and halt disease progression by reducing intraosseous pressure and promoting revascularisation. Despite its potential benefits, the variable success rates reported in the literature underscore the need for further investigation into adjuvant therapies to optimise outcomes.
Bisphosphonates, known for their anti-resorptive properties and positive effects on bone metabolism, have shown promise as an adjunctive treatment in AVNFH.2 Alendronate, a bisphosphonate, has demonstrated its efficacy in improving bone density and reducing the risk of fractures in osteoporosis.3 However, the role of bisphosphonate therapy in conjunction with core decompression for AVNFH management remains an active research area.
This proposed randomised control trial seeks to contribute to the existing body of knowledge by rigorously evaluating the combined use of core decompression and bisphosphonate therapy to manage early AVNFH. Drawing on the foundational work of Steinberg and colleagues,4 who highlighted the importance of early intervention and the potential benefits of bisphosphonates, this study aims to provide valuable insights into the comparative effectiveness of these treatment modalities.
By elucidating the optimal approach to early AVNFH management, this research can enhance clinical decision-making and improve patient outcomes in a population susceptible to significant morbidity. The study’s foundation rests on the compelling need to address the challenges posed by AVNFH, emphasising the potential impact of a tailored, multidisciplinary treatment approach.
Aim
To evaluate the efficacy and safety of Core Decompression in managing early Avascular Necrosis of the femoral head, comparing outcomes with or without adjuvant bisphosphonate therapy.
Primary objective
To determine the impact of Core Decompression with bisphosphonate therapy compared to Core Decompression alone on the overall functional outcomes in patients with early-stage Avascular Necrosis of the femoral head, as measured by changes in the Harris Hip Score.
Secondary objectives
1. To assess and compare the reduction in pain levels between the two treatment groups using the Visual Analogue Scale (VAS).
2. To evaluate and compare the radiographic changes in the femoral head in patients undergoing Core Decompression with bisphosphonate therapy versus Core Decompression alone.
3. To analyze and compare the incidence of complications and adverse events between the two treatment groups.
Methods
Study setting
The study will be conducted at Jawaharlal Nehru Medical College and Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, in the Department of Orthopedics. The study will follow a prospective interventional design, with data collection from July 2022 to July 2024 and data analysis scheduled for August 2024 to September 2024.
Inclusion criteria
1. Skeletally Mature Patients: Adults who have reached skeletal maturity will be eligible for inclusion.
2. Avascular Necrosis of Femoral Head (AVNFH): Patients diagnosed with Avascular Necrosis of the femoral head in stage 1 and stage 2, irrespective of the aetiology.
3. Willingness to Undergo Surgery: Patients willing to undergo surgical intervention for inclusion in one or both hips.
Exclusion criteria
1. Previously Operated Hips: Patients with previous hip surgeries will be excluded.
2. Arthritic Changes in Involved Hip: Cases presenting with arthritic changes in the involved hip joint will be excluded.
3. Unwillingness for Surgery: Patients unwilling to undergo the prescribed surgical intervention.
Interventions
Patients meeting the inclusion criteria will be randomised into two groups:
Group 1: Core Decompression with Bisphosphonate Therapy Patients in this group will undergo core decompression surgery combined with bisphosphonate therapy.
Core Decompression Procedure
1. Preoperative Antibiotic Prophylaxis: Ceftriaxone antibiotic for 24 hours (3 doses) post-surgery to prevent infection.
2. Analgesic Regimen: Analgesics will be prescribed for five days postoperatively to manage pain.
3. Calcium and Vitamin Supplementation: Calcium and vitamin supplements will be provided for one-month post-surgery to support bone healing.
4. Bisphosphonate Therapy: Alendronate (70 mg) will be administered once weekly for nine months for odd-numbered participants in this group.
Group 2: Core Decompression Alone Patients in this group will undergo core decompression surgery without bisphosphonate therapy.
Core Decompression Procedure
1. Preoperative Antibiotic Prophylaxis: Similar to Group 1, ceftriaxone antibiotic for 24 hours (3 doses) post-surgery.
2. Analgesic Regimen: Similar to Group 1, analgesics will be prescribed five days postoperatively.
3. Calcium and Vitamin Supplementation: Similar to Group 1, calcium and vitamin supplements will be provided for one-month post-surgery.
Outcomes
Primary outcome
The study’s primary outcome is the comparison of overall functional outcomes between the two intervention groups, as measured by changes in the Harris Hip Score5 at the defined followup time points (6 weeks, three months, six months, and nine months). The Harris Hip Score assesses pain, function, absence of deformity, and range of motion, providing a comprehensive evaluation of hip joint health.
Secondary outcomes
1. Pain Reduction (Visual Analogue Scale - VAS)6: Comparison of pain levels between the two groups using the Visual Analogue Scale at each followup visit. This assessment will provide insights into the immediate and sustained pain relief the interventions achieve.
2. Radiographic Changes in Femoral Head: Evaluation of radiographic changes in the femoral head using X-ray and MRI at each followup visit. This will include assessing structural changes, necrotic areas, and the progression or resolution of Avascular Necrosis.
3. Complications and Adverse Events: Monitoring and comparison of the incidence of complications and adverse events in both intervention groups. This will include surgical complications, bisphosphonate-related side effects, and any unexpected events affecting patient outcomes.
Sample size calculation
This means 29 or more measurements/surveys are needed to have a confidence level of 95% that the real value is within ±5% of the measured/surveyed value. Prevalence of AVN taken.7
Recruitment
1. Identification of Potential Participants: Patients presenting with hip pain at the Department of Orthopedics, Jawaharlal Nehru Medical College, and Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, will be screened for potential inclusion.
2. Clinical Evaluation: Patients with suspected Avascular Necrosis of the femoral head will undergo a thorough clinical evaluation, including history, physical examination, and relevant investigations.
3. Radiological Assessment: Radiological assessments, including X-ray and MRI, will be performed to confirm the diagnosis and stage of the Avascular Necrosis. Only patients in stage 1 and stage 2 will be considered for inclusion.
4. Informed Consent: Eligible patients will be provided detailed information about the study, its objectives, interventions, and potential risks and benefits. Informed consent will be obtained from those willing to participate.
5. Randomization: Randomization will be conducted using a simple randomisation method to allocate participants into either the Core Decompression with Bisphosphonate Therapy or the Core Decompression Alone group.
6. Baseline Assessments: Baseline assessments, including demographic details, medical history, and baseline clinical and radiological data, will be collected from enrolled participants.
7. Surgical Intervention: Participants will undergo the assigned surgical intervention according to the randomisation. Core decompression with or without bisphosphonate therapy will be performed based on the allocated group.
8. Postoperative Care: Participants will receive postoperative care according to the defined protocol, including antibiotic prophylaxis, analgesics, and supplementary medications.
9. Follow-up Visits: Participants will be scheduled for followup visits at six weeks, three months, six months, and nine months postoperatively for clinical and radiological assessments.
10. Data Collection: Clinical, radiological, and laboratory data will be collected at each followup visit to assess the predefined outcomes.
Allocation
The allocation of participants into the two intervention groups, Core Decompression with Bisphosphonate Therapy and Core Decompression Alone, will be performed using a simple randomisation method. Randomisation aims to minimise selection bias and ensure that each participant has an equal chance of being assigned to either group, thus promoting the validity of the study results.
Blinding
Given the nature of the interventions, it may be challenging to blind the participants and the surgical team to the assigned treatment. However, efforts will be made to minimise bias in the assessment of outcomes through the following strategies:
1. Blinding of Outcome Assessors: Individuals responsible for collecting and assessing primary and secondary outcome measures, such as Harris Hip Score, Visual Analogue Scale, and radiographic evaluations, will be blinded to the treatment allocation. This blinding will help minimise potential bias in outcome assessments.
2. Data Analysis Blinding: Data analysis will be conducted by individuals who must be aware of the treatment allocation. Coding or labelling of treatment groups will be used to blind the statisticians involved in data analysis.
3. Blinding of Participants: While blinding participants may be challenging due to the nature of the surgical interventions, efforts will be made to minimise participant bias by emphasising the importance of objective reporting during followup assessments.
Data collection process
The data collection process for the randomised control trial on managing early avascular necrosis of the femoral head will involve a systematic approach to gathering relevant information at various stages of the study. The data collection process includes the following steps:
1. Preoperative Data Collection:
• Clinical Assessment: Demographic details, medical history, and baseline clinical information will be recorded, including age, sex, risk factors, and duration of the illness.
• Radiological Assessment: X-ray (AP pelvis with Both hip and Lateral view of the affected hip) and MRI (pelvis with both hips) will be performed for staging AVNFH using the FICAT-ARLET classification.
2. Randomization and Intervention:
• Randomization will be conducted, and participants will be allocated to either the Core Decompression with Bisphosphonate Therapy group or the Core Decompression Alone group.
• Surgical interventions will be performed according to the assigned group, and data related to the surgical procedure will be documented.
3. Intraoperative Data Collection:
4. Postoperative Care:
5. Laboratory Data:
6. Follow-up Visits:
• Participants will be scheduled for followup visits at six weeks, three months, six months, and nine months postoperatively.
• Clinical data will be collected at each followup, including pain assessment using the Visual Analogue Scale (VAS),8 range of motion, tenderness, ability to walk, and any signs of instability.
• Radiological assessments will be performed at each followup, with an X-ray and MRI if needed.
7. Bisphosphonate Administration (for Odd-numbered Groups):
8. Data Validation and Quality Control:
9. Data Analysis:
Data management
Effective data management is crucial to ensure the accuracy, security, and integrity of study data throughout the randomised control trial on managing early Avascular Necrosis of the femoral head.
1. Data Collection Tools: Standardized and pre-printed data collection forms will record information consistently. Electronic data capture systems may also be employed for efficient data management.
2. Data Entry: Double data entry will be performed to minimise errors. Data entered electronically or manually will be validated to identify discrepancies and ensure consistency.
3. Data Storage: All collected data will be securely stored in a designated database or file system. Access to the database will be restricted to authorised personnel to maintain confidentiality.
4. Data Security: Strict measures will be implemented to safeguard the confidentiality and integrity of participant data. Password protection, encryption, and regular backup procedures will be employed.
5. Data Monitoring: Periodic data monitoring will be conducted to identify and rectify any inconsistencies, missing data, or outliers. Any changes or corrections to the data will be documented with appropriate justifications.
6. Quality Control: Quality control procedures will be established to ensure the accuracy and reliability of the collected data. This includes routine checks for completeness, accuracy, and adherence to the study protocol.
7. Data Confidentiality: Participant confidentiality will be maintained by assigning unique identifiers rather than using participant names in the dataset. Access to identifiable information will be restricted to authorised personnel.
8. Data Sharing Policy: Data sharing will be governed by institutional policies and ethical considerations. Access to the dataset may be granted to specific individuals or entities based on predefined criteria.
9. Data Analysis: Data analysis will be conducted using statistical software, and the results will be reported in a manner that preserves the anonymity of participants.
10. Data Archiving: Upon completion of the study, all relevant study documents and datasets will be archived according to institutional and regulatory requirements.
Statistical method
The statistical analysis for the randomised control trial on managing early Avascular Necrosis of the femoral head will employ a comprehensive approach to evaluate the effectiveness of Core Decompression with Bisphosphonate Therapy compared to Core Decompression Alone. Descriptive statistics will summarise demographic characteristics and compare baseline characteristics between groups to assess randomisation success. The primary outcome, changes in the Harris Hip Score over time, will undergo repeated measures analysis of variance or a mixed-effects model. Secondary outcomes, including pain reduction, radiographic changes, complications, and patient satisfaction, will be analysed using appropriate statistical tests. Subgroup analyses may explore variations in treatment effects based on etiological factors. Survival analysis methods may be applied for time-to-event outcomes. Missing data will be handled using imputation methods, and a significance level of 0.05 will be used for hypothesis testing using SPSS version 23. Data visualisation techniques will aid in interpreting trends, and, if applicable, the Data Safety Monitoring Board will review safety and efficacy data at predetermined intervals. The analysis plan, outlined in the study protocol, will guide the statistical methods to ensure a rigorous and meaningful evaluation of the interventions’ impact on Avascular Necrosis of the femoral head management.
Ethical considerations
Ethical Considerations and Ancillary/Post-Trial Care
Approval and Informed Consent: The Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) has approved the study protocol (Reference number: DMIHER (DU)/IEC/2022/45, Date: 18-07-2022). Additionally, the trial is registered with the Clinical Trials Registry – India (CTRI/2023/09/057253). Before study initiation, written informed consent will be obtained from all participants or their legal guardians, ensuring they are fully informed about the study’s objectives, procedures, potential risks, and benefits.
Ancillary/Post-Trial Care
Upon the conclusion of the randomised control trial on the management of early Avascular Necrosis of the femoral head, a thorough plan for ancillary and post-trial care will be executed to safeguard the participants’ well-being and ensure the ethical closure of the study. Participants will be informed about the trial’s completion, and details regarding continued medical care and followup appointments will be provided. A post-trial monitoring period will be instituted to assess long-term outcomes and potential complications, with participants monitored for an extended duration to detect any delayed effects or adverse events. Referral pathways and contact information for relevant healthcare providers will be given to facilitate ongoing care for participants requiring further attention. Participants will retain access to trial-related information, including their data, upon request, promoting transparency and addressing any queries or concerns. A summary of the trial results will be shared with participants, fostering transparency and respect in the researcher-participant relationship. Counselling services will be available to address emotional or psychological aspects of participation. Contact information for study coordinators or principal investigators will be provided for an extended period to allow participants to seek clarification or ask questions even after the trial’s completion. Data collected during the trial will be securely stored for an appropriate period, with procedures for data access outlined to protect participant confidentiality. Ethical oversight will persist beyond the trial’s completion, ensuring ongoing consideration of ethical considerations and participant welfare. This comprehensive plan underscores the commitment to ethical research conduct and prioritises the well-being of study participants.
Dissemination
After the completion of the study, we will publish it in an indexed journal or conference.
Discussion
The proposed randomised control trial investigating the management of early Avascular Necrosis of the femoral head (AVNFH) through core decompression with and without bisphosphonate therapy addresses a critical gap in our understanding of optimal treatment strategies for this debilitating condition. Avascular Necrosis, often associated with significant morbidity and impaired quality of life, necessitates effective interventions to mitigate its progression and impact on hip joint function.
The rationale for combining core decompression with bisphosphonate therapy stems from the multifaceted nature of AVNFH, involving both mechanical and metabolic factors. By reducing intraosseous pressure and promoting revascularisation, core decompression has shown promise in alleviating symptoms and preserving joint function.9 Bisphosphonates, recognised for their anti-resorptive properties, have the potential to modulate bone metabolism and enhance the reparative processes within the femoral head.2
This proposal is grounded in the broader context of AVNFH management, drawing insights from existing literature and pioneering studies. The work of Agarwala et al.,2 which demonstrated the efficacy of alendronate in AVNFH treatment, is a foundational reference supporting the potential benefits of bisphosphonate therapy. Additionally, the quantitative staging system proposed by Steinberg et al.4 contributes to understanding AVNFH severity, aiding in patient stratification and treatment decision-making.
The proposed study aims to build upon these foundations by systematically evaluating the combined approach of core decompression and bisphosphonate therapy. By incorporating patient-reported outcomes, radiographic assessments, and well-established measures such as the Harris Hip Score, the study aims to comprehensively understand treatment effectiveness and its impact on patients’ functional outcomes. However, the proposed trial also raises several considerations and potential challenges. If previous studies suggest its efficacy, ethical concerns surrounding including a control group without bisphosphonate therapy will be carefully addressed to ensure participant well-being. Additionally, the study’s generalizability may be influenced by the specific characteristics of the study population and variations in etiological factors contributing to AVNFH.
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CITE
how to cite this article
Lohiya A and Dhaniwala N. Randomised control trial on management of early avascular necrosis of femoral head by core decompression with bisphosphonate therapy versus core decompression in tertiary care hospital in central India [version 1; peer review: 1 approved with reservations]. F1000Research 2024, 13:398 (https://doi.org/10.12688/f1000research.146853.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Version 1
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PUBLISHED 26 Apr 2024
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How to cite this report:
Hailer YD. Reviewer Report For: Randomised control trial on management of early avascular necrosis of femoral head by core decompression with bisphosphonate therapy versus core decompression in tertiary care hospital in central India [version 1; peer review: 1 approved with reservations]. F1000Research 2024, 13:398 (https://doi.org/10.5256/f1000research.160976.r285859)
The direct URL for this report is:
https://f1000research.com/articles/13-398/v1#referee-response-285859
https://f1000research.com/articles/13-398/v1#referee-response-285859
NOTE: it is important to ensure the information in square brackets after the title is included in this citation.
Reviewer Report 12 Jun 2024
Approved with Reservations
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Thank you for allowing me to review the study.
The researchers aim to study the effect of Core Decompression with and without Bisphosphonate Therapy in managing early Avascular Necrosis of the femoral head of skeletally mature patients. ... Continue reading
The researchers aim to study the effect of Core Decompression with and without Bisphosphonate Therapy in managing early Avascular Necrosis of the femoral head of skeletally mature patients. ... Continue reading
CITE
HOW TO CITE THIS REPORT
Hailer YD. Reviewer Report For: Randomised control trial on management of early avascular necrosis of femoral head by core decompression with bisphosphonate therapy versus core decompression in tertiary care hospital in central India [version 1; peer review: 1 approved with reservations]. F1000Research 2024, 13:398 (https://doi.org/10.5256/f1000research.160976.r285859)
The direct URL for this report is:
https://f1000research.com/articles/13-398/v1#referee-response-285859
https://f1000research.com/articles/13-398/v1#referee-response-285859
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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