Efficacy of a Combination of Ultrasound-guided Intra-articular Injections of Hyaluronic Acid, High-power Laser Therapy and Rehabilitation on Functioning in Patients Affected by Hip Osteoarthritis: a Randomized Controlled Trial
Phase: NA
Conditions: Hip Osteoarthritis
Sponsor: De Sire Alessandro

NCT number 429/2021, 13/06/2025 
 
Effectiveness of a Next-Generation High-Power Laser Treatment 
Combined with Intra-Articular Injection of Hyaluronic Acid (HA) and 
Physiotherapy in Reducing Pain in Patients with Hip Osteoarthritis: A 
Randomized Controlled Clinical Trial 
Type of Research (Setting) 
☒ Single-center 
☐ Multicenter 
Type of Research (Design) 
☒ Interventional study (RCT or similar) 
☐ Retrospective observational study 
☐ Prospective observational study 
☐ Cross-sectional observational study 
☐ Systematic literature review 
☐ Non-systematic literature review 
☐ Case series 
☐ Single case study 
☐ Proposal of new decision-making algorithms 
Introduction 
Osteoarthritis is one of the most common diseases of our time. It affects the entire joint and 
is characterized by progressive cartilage loss, subchondral bone erosion, and damage to 
muscles and ligaments. The hip is a ball-and-socket joint that plays a critical role in weight 
bearing. During standing, walking, and running, the hip joint is subjected to static and 
dynamic forces that predispose the femur and acetabulum to chronic wear. Hip 
osteoarthritis (OA) is the leading cause of musculoskeletal disability in developed countries 
and one of the most common causes of limitations in daily activities among the adult 
population. 
 
UNIVERSITA’ DEGLI STUDI DI CATANZARO 
“MAGNA GRÆCIA” 
SCUOLA DI MEDICINA E CHIRURGIA 
DIPARTIMENTO DI SCIENZE MEDICHE  E CHIRURGICHE 
AZIENDA OSPEDALIERA “ MATER DOMINI”                                                                                     
_____________________________________________________________________________________________________________________ 

NCT number 429/2021, 13/06/2025 
 
Diagnosis of coxarthrosis is often clinical, although radiographic investigations are useful 
for confirming and monitoring disease progression. The most widely used radiographic 
grading system for OA is the Kellgren and Lawrence (K&L) scale, ranging from 0 to 4, with 
grades 2 or higher indicating radiographic OA. Higher K&L grades reflect greater joint space 
narrowing, osteophyte presence, and subchondral sclerosis. Notably, there can be 
significant discordance between symptoms and radiographic findings. 
 
Management of coxarthrosis includes educational, behavioral, psychosocial, 
physiotherapeutic, pharmacological, and physical therapy interventions. Physiotherapy is a 
cornerstone of conservative treatment, showing considerable effects on pain and disability. 
Intra-articular treatments, particularly with hyaluronic acid (HA), are also effective for 
reducing pain and improving function. 
 
In OA joints, pro-inflammatory cytokines and proteases disrupt HA synthesis, reducing 
synovial fluid viscoelasticity. Exogenous HA injections improve synovial viscosity. 
Study Objectives 
The primary outcome of this randomized controlled trial (RCT) is to assess the effectiveness 
of a combined treatment consisting of intra-articular HA injections, high-power laser 
therapy, and standard physiotherapy in improving hip function in patients with 
coxarthrosis. Secondary outcomes include pain reduction, changes in hip joint range of 
motion (ROM), strength of the hip flexor and extensor muscles, and disability related to the 
pathology. 
Materials and Methods 
Participants 
Patients with hip osteoarthritis will be recruited at the Complex Operative Unit of Physical 
and Rehabilitation Medicine of the Mater Domini University Hospital of Catanzaro starting 
from January 2022. 
Inclusion Criteria: 
- Age >18 years 
- Diagnosis of hip osteoarthritis (stage ≤ 3 according to Kellgren and Lawrence 
classification) 
- Hip pain with Numeric Rating Scale (NRS) ≥ 4 
- Body mass index <30 kg/m² 
- Patients willing to discontinue NSAIDs, opioids, corticosteroids, muscle relaxants, or any 
therapy that could interfere with study evaluations, and agree not to resume such therapies 
during the study period 

NCT number 429/2021, 13/06/2025 
Exclusion Criteria: 
- Severe cognitive decline (Mini-Mental State Examination score <24) and/or inability to 
provide informed consent 
- Concurrent treatment with anti-inflammatory drugs or rehabilitative therapies 
- Rheumatoid arthritis 
- Previous hip replacement 
- Planned lower limb surgeries within 6 months 
- Oral analgesic therapy, intra-articular injections, physiotherapy, and/or instrumental 
physical therapy within the past 30 days 
- History of neurological or psychiatric disorders 
- Hemorrhagic diathesis 
- Pacemaker users 
- Oncological diseases 
- Pregnancy or breastfeeding 
- History of epilepsy 
- Ongoing infectious diseases 
Only patients who sign the informed consent for personal data processing, after reading the 
written information and understanding both the written and oral explanations provided by 
study staff, will be included. Patients will also be informed of their rights in accordance with 
Article 7 of Legislative Decree 30/06/2003, No. 196 (Privacy Code). 
Intervention 
At baseline (T0), enrolled patients will be randomly allocated (1:1 ratio) into two treatment 
groups: 
 
- Study Group: 2 ultrasound-guided weekly intra-articular injections with Hymovis 
Hyaluronic Acid (HYADD 4) 24mg/3ml, followed by 10 sessions of standard rehabilitative 
treatment (5 sessions/week for 2 weeks), consisting of passive and active kinesitherapy, 
stretching and strengthening exercises (45 minutes each), combined with 10 sessions of 
high-power laser therapy (5 sessions/week for 2 weeks) using Laserix Pro. 
 
- Control Group: same protocol as the study group, except that the laser therapy will be 
replaced with 10 sessions of sham laser therapy using the same device. 
Blinding 
Patients and the physician responsible for outcome evaluations will be blinded to group 
allocation. The physiotherapist administering the intervention will not participate in the 
outcome assessment. 
Primary Outcome 
Harris Hip Score to assess hip functionality. 

NCT number 429/2021, 13/06/2025 
Secondary Outcomes 
- Reduction of pain in the hip joint, assessed by the Numeric Rating Scale (NRS), with a score 
from 0 (no pain) to 10 (worst pain ever experienced). 
- Improvement in hip joint range of motion (ROM) for: 
  • Abduction and Adduction (Right and Left) 
  • Flexion-Extension (Right and Left) 
- Manual Muscle Testing (MMT) to evaluate lower limb muscle strength 
- Balance and gait assessed by the Tinetti Scale 
- Six-Minute Walking Test (6MWT) to evaluate performance 
- Health-Related Quality of Life (HRQoL) measured by the EuroQol 5 Dimensions 3 Levels 
Index (EQ5D3L Index) 
Time-Points 
T0: Baseline 
T1: End of treatment 
T2: 3 months after the first visit 
T3: 6 months after the first visit 
T4: 12 months after baseline 
Sample Size 
For sample size calculation, a non-Gaussian distribution of variables was assumed, 
considering the difference in pain score reduction between the two groups as the primary 
outcome. Given the exceptional nature of the study, the total sample size will be 15 patients 
per group. Assuming a hypothetical dropout rate of 10%, 34 participants will be required 
(17 per group). 
References 
1. Sandiford NA et al. Osteoarthritis of the hip: aetiology, pathophysiology and current 
aspects of management. 2020. 
2. De Pieri E et al. Subject-Specific Modeling of Femoral Torsion... Front Bioeng 
Biotechnol. 2021. 
3. Dagenais S et al. Systematic review of radiographic primary hip OA. Clin Orthop 
Relat Res. 2009. 
4. Murphy NJ et al. Hip Osteoarthritis: Etiopathogenesis... Adv Ther. 2016. 
5. Croft P et al. Defining osteoarthritis of the hip... Am J Epidemiol. 1990. 
6. Pereira D et al. Effect of OA definition on prevalence... Osteoarthritis Cartilage. 2011. 
7. Kolasinski SL et al. 2019 ACR/AF Guideline for OA. Arthritis Care Res. 2020. 

NCT number 429/2021, 13/06/2025 
8. Fernandes L et al. EULAR recommendations for non-pharmacological management. 
Ann Rheum Dis. 2013. 
9. Kraus VB et al. Physical Activity in Knee and Hip OA. Med Sci Sports Exerc. 2019. 
10. Bennell KL et al. Physical Therapy in Hip OA: RCT. JAMA. 2014. 
11. Dallari D et al. PRP and HA injections for hip OA. Am J Sports Med. 2016. 
12. Piccirilli E et al. Viscosupplementation with HA. MLTJ. 2016. 
13. Angelova A, Ilieva EM. High Intensity Laser Therapy. Pain Res Manag. 2016. 
14. Nazari A et al. High-intensity laser vs physiotherapy. Lasers Med Sci. 2019. 
15. Kheshie AR et al. High- vs low-level laser therapy. Lasers Med Sci. 2014. 
16. Ip D, Fu NY. Low-level lasers + HA prolong joint function. Clin Interv Aging. 2015. 
 

 
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NCT number 429/2021. 13/06/2025 
UNIVERSITA’ DEGLI STUDI DI CATANZARO 
“MAGNA GRÆCIA” 
SCUOLA DI MEDICINA E CHIRURGIA 
DIPARTIMENTO DI SCIENZE MEDICHE  E CHIRURGICHE 
AZIENDA OSPEDALIERA “ MATER DOMINI”                                                                                     
_____________________________________________________________________________________________________________________ 
INFORMED CONSENT FOR THE STUDY: 
Efficacy of a combined rehabilitative treatment with intra-articular hyaluronic acid injection and 
high-power laser therapy in improving hip function in patients affected by coxarthrosis: a 
randomized controlled clinical trial. 
 
I, the undersigned, _______________________________________________________________ 
born 
in 
________________________________ 
on 
______________ 
and 
residing 
at 
________________________________________________, declare that I am aware of my medical 
condition (Coxarthrosis). 
I have been offered participation in an experimental clinical study at the Physical Medicine and 
Rehabilitation Unit of the Mater Domini University-Hospital of Catanzaro, which involves 
combined treatment with intra-articular hyaluronic acid injection, high-power laser therapy, and 
physiotherapy. The actual usefulness of this treatment, the possible outcomes, expected benefits, 
potential complications and local and/or general side effects, as well as the possibility of failure 
have been clearly explained to me. 
 
The treatment procedures have been illustrated to me, which include my random assignment to one 
of the treatment groups as follows: 
 
a cycle of 2 ultrasound-guided injections at weekly intervals into the hip joint with Hyaluronic 
Acid, 10 sessions of standard rehabilitative treatment (5 sessions/week for 2 weeks) lasting 45 

 
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NCT number 429/2021. 13/06/2025 
UNIVERSITA’ DEGLI STUDI DI CATANZARO 
“MAGNA GRÆCIA” 
SCUOLA DI MEDICINA E CHIRURGIA 
DIPARTIMENTO DI SCIENZE MEDICHE  E CHIRURGICHE 
AZIENDA OSPEDALIERA “ MATER DOMINI”                                                                                     
_____________________________________________________________________________________________________________________ 
minutes each, followed by 10 concomitant sessions (5 sessions/week for 2 weeks) of laser therapy 
(20 minutes); 
or 
 
a cycle of 2 ultrasound-guided injections at weekly intervals into the hip joint with Hyaluronic 
Acid, 10 sessions of standard rehabilitative treatment (5 sessions/week for 2 weeks) lasting 45 
minutes each, followed by 10 concomitant sessions (5 sessions/week for 2 weeks) of “sham” laser 
therapy (20 minutes), during which my clinical and functional conditions will also be evaluated. 
 
Follow-up checks are also planned. During the consultation with the Medical and Physiotherapy 
Staff, I received all the explanations requested for a full understanding of the treatment and had 
sufficient time to reflect on the information received, so as to give informed consent. I declare that I 
am fully aware, that I have carefully read this document, and that I have understood every part and 
its meaning. 
Consent is personal and cannot be delegated to family members. 
 
The undersigned ________________________________________________ declares to have 
received from Dr./Ms. __________________________________________ exhaustive, realistic, 
understandable, and clear information regarding the treatment and possible side effects and declares 
the willingness to participate in the study. 
 
Read and signed _____________________ 

 
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NCT number 429/2021. 13/06/2025 
UNIVERSITA’ DEGLI STUDI DI CATANZARO 
“MAGNA GRÆCIA” 
SCUOLA DI MEDICINA E CHIRURGIA 
DIPARTIMENTO DI SCIENZE MEDICHE  E CHIRURGICHE 
AZIENDA OSPEDALIERA “ MATER DOMINI”                                                                                     
_____________________________________________________________________________________________________________________ 
 
The Patient _____________________________ 
The Doctor _____________________________