Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04251832 |
| Other study ID # |
STShoulderPain |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2020 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
September 2021 |
| Source |
Unidade Local de Saúde do Alto Minho |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Calcific tendinitis of the rotator cuff is one of the most common causes of shoulder pain.
Ultrasound guided percutaneous lavage (UGPL or barbotage or irrigation) of calcific
tendinopathy is indicated when conservative treatments (physiotherapy, nonsteroidal
anti-inflammatory drugs) have failed. Our hypothesis is that lavage followed by intra-calcic
injection of STS could fasten the dissolution of the calcific deposit. In view of the short
half-life of this molecule the investigators hypothesize that this would happen within the
first month after the procedure. Therefore, the investigatorschose to assess our primary
objective at 1 month. Few studies have evaluated the short-term radiographic evolution after
lavage.
Description:
Calcific tendinitis of the rotator cuff is one of the most common causes of shoulder pain. It
is characterized by calcium phosphate crystal deposition in the rotator cuff. Its
pathogenesis and etiology remains unclear and the mechanisms leading to this pathological
mineralization are still largely unknown. This disorder can lead to a chronic pain during
daily or professional activities and to a restriction of range of motion. During the disease,
spontaneous resorption can occur with migration of apatite crystals into the subacromial
bursa causing severe pain and restriction of movement. Factors associated with the
development of symptoms are still unclear although the size and presence of a bursitis on
imaging have been shown to be associated with pain.
Ultrasound guided percutaneous lavage (UGPL or barbotage or irrigation) of calcific
tendinopathy is indicated when conservative treatments (physiotherapy, nonsteroidal
anti-inflammatory drugs) have failed. At this stage, extracorporeal shock wave therapy (ESWT)
or subacromial corticosteroid injection can also be discussed. However, a recent network
meta-analysis has shown that UGPL could be the treatment of choice compared to the other
nonsurgical options such as ESWT or SAI. Arthroscopic removal of the calcific deposit is
considered as a second line therapy after failure of UGPL or EWST.
Efficacy of UGPL depends on the type of calcification. Calcific deposits can be
differentiated in hard calcifications, usually dense on X-Ray with an acoustic shadow on US,
and soft calcifications, with more heterogeneous or faint contours without acoustic
shadowing. Some studies observed failure only in patients presenting with a dense and
homogeneous calcification type A according to the Molé Classification and also showed that
outcome after needling and/or ESWT will be worse in case of dense calcifications, with only
30% of success compared to 61% in patients with soft calcification. These failures are most
of the time explained by the persistence of the calcific deposit. In line with this, was
found a positive correlation between the decrease of the size of the calcification and the
pain score over time; as the calcification became smaller, the pain became less intense.
Several approaches are currently used to facilitate the extraction of the calcification. It
has been shown that lavage with warm saline heated at 42°C reduced the procedure duration and
improved calcification dissolution. Another randomized controlled study recently reported
that lavage with a 2 needle approach also shortened the procedure in hard calcification.
However, none of these studies showed an impact on the rate of calcification elimination.
Other strategies are therefore needed to treat hard calcification of the rotator cuff.
Sodium thiosulfate (STS) (Na2S2O3) is primarily used to prevent and treat cyanide poisoning.
Intravenous STS is also used off-label to treat calciphylaxis leading to a significant
decrease of soft-tissue and vascular calcifications. However, its systemic use may be limited
by adverse effects, such as gastrointestinal upset, metabolic acidosis, and sodium overload.
Thus, alternative local approaches have been developed. Recent reports have shown the
interest of topical STS in the treatment of calciphylaxis, tumoral calcinosis associated with
connective tissue disease, pseudohypoparathyroidism or hyperphosphatemic familial tumoral
calcinosis. For instance, a daily application of topical STS on the calcific lesions of
patients with hyperphosphatemic familial tumoral calcinosis led to their decrease after 5
months of treatment. Topical application of STS has also showed an anti-inflammatory effect
in patients with calcinosis cutis secondary to connective tissue disease and radiodermatitis.
Because deeper calcific deposits are unlikely to be reached by topical therapeutic agents,
some authors performed intralesional STS injections in patients with localized cutaneous
calciphylaxis. They observed a complete healing of ulcers and remission of disease with only
transient localized discomfort during injection. Despite these promising results, the exact
mechanisms by which STS is able to dissolve ectopic calcifications remain still unclear.
Recently one study showed that STS was well tolerated with no side effect occurring during
ultrasound-guided percutaneous lavage of calcific tendinopathy.
These preliminary results prompted us to study the interest of STS in the treatment of
calcific tendinitis. As dense calcifications are associated with higher risk of failure of
UGPL, the investigators will select patients to perform a lavage followed by an intralesional
injection of STS. The objective of our study is to evaluate the efficacy of sodium
thiosulfate lavage in the treatment of shoulder pain in calcific tendinitis. the
investigators will also assess its effect on clinical symptoms and radiographic evolution of
the calcific deposit and hypothesize that sodium thiosulfate would be well-tolerated and
fastened the elimination of the calcific deposit in patients with dense calcifications.
METHODS The current study is a prospective, monocentric, phase II, single group, open label
study.
Study population The investigators will include patients referred to the rheumatology
department for the treatment of a shoulder pain calcific tendinitis. Inclusion criteria are
the following: age over 18 years old; pain for more than 3 months; worsening of symptoms with
activities above shoulder level; minimum one the 3 following impingement positive clinical
tests (Yocum, Hawkins, Neer); calcification > 5 mm in size on the standard anteroposterior
(AP) radiographs. Only type A calcification according the Molé Classification will be
included. The exclusion criteria will be: allergy to sodium metabisulfite, asthma, chronic
renal disease (creatinine clearance <30 ml/min), Type B or C calcification according the Molé
Classification, other shoulder disease (glenohumeral or acromioclavicular osteoarthritis,
rotator cuff tear, rheumatoid arthritis); previous percutaneous irrigation of the same
calcification.
Baseline clinical, radiological and ultrasonographic evaluation The investigators will
recorde the main demographic characteristics: medical history, occupation, dominant hand,
presence of nocturnal pain, and day off-work because of the shoulder pain. VAS pain at rest
and during activities, shoulder range of motion, DASH score, and EQ5D quality of life VAS
score will also be recorded. X-Ray of the affected shoulder will be performed
(anteroposterior view in neutral, internal and external rotation and lateral scapula view).
Calcifications types will be classified according to Molé at al (A: dense, well defined and
circumscribed; B: dense, well-defined and segmented; C: transparent and nonhomogeneous).
Surface of the calcification will be measured on the view where the calcification appears the
largest. The same view will be used for all measurements during follow-up. Density of the
deposit will be evaluated on the same view. All the measurements will be made by an
experienced rheumatologist (with 35 years' experience in clinical radiologic evaluation)
blinded from the clinical status (ABV).
US evaluation of the affected shoulder will be performed using a GE LogiS8 using a 6-15 MHz
linear probe. The investigators will be recorded the maximum size of the calcic deposit in
axial and longitudinal view. Calcific shoulder plaques will be classified into 4 types based
on their morphology, as previously described. Arc-shaped (an echogenic arc .with clear
shadowing); 2. Fragmented or punctate (at least 2 separated echogenic spots or plaques) with
shadowing); 3. Fragmented or punctate without shadowing; 4. Nodular (an echogenic nodule
without shadowing). Presence of a bursitis (>2 mm thickening of the SAB) and power Doppler
signal in and around the calcification will be recorded. For power Doppler imaging, the pulse
repetition frequency will be set at 2.4 cm/s and the color gain at the most sensitive level
before the appearance of noise. The color flow signal intensity will be graded on a scale of
0 to 3, where 0 represents no signal, 1 = mild (weak, spot-like color flow signal), 2 =
moderate (a few rod-like color flow signals), and 3 = severe (multiple rod-like or linear
color flow signals).
Intervention All patients will be undergoing a baseline clinical, X-Ray and US evaluation by
rheumatologists with 11 years and 5 years' experience in US and US-guided interventions.
Patients will be with a US-guided single needle technic. After sterile preparation, local
anesthesia will be performed under US guidance. A total of 10 mL of lidocaine 1% will be
injected in the subcutaneous tissues, the subacromial bursa and over the surface of the
calcific deposit. A 21 G pediatric spinal needle will be used for the procedure to prevent
needle clogging by calcific debris. Indeed, introduction of the needle with the stylet
prevents the needle to be clogged. Once the needle tip will be inside the calcification, the
stylet will be removed, and the lavage could start. When backflow of calcific material could
be identified in the syringe, lavage of the deposit will be performed using sodium
thiosulfate 25 %: a volume of 1 mL of sodium thiosulfate will be prepared in a syringe and
successive propulsion and aspiration will be performed. The procedure will be repeated until
the backflow becomes clear. At the end of the procedure 1 mL (250 mg) of thiosulfate will be
injected inside the calcific deposit. Finally, 1.5 mL of methylprednisolone will be injected
in the SAB.
X-Ray of the shoulder will be performed just after the procedure. Patients will be treated
with diclofenac (75 mg LP twice daily) and paracetamol (1000 mg, 4 times a day) for 48 hours
then only if needed. Routine use of the shoulder will be allowed without restrictions and all
patients had one week off-work.
Follow-up All patients will have follow-up visits at 1 week, 1 month and 3 months after
intervention. At each time point, VAS pain at rest and during activities, shoulder range of
motion, and DASH score will be recorded. EQ5D quality of life VAS score will be also
recorded. X-Ray of the affected shoulder will be performed at each time point and evaluated
as previously described. Care will be taken to use the exact same settings (mAs;kV) to allow
a proper comparison of the calcific deposit between each evaluation. The evolution of the
calcific deposit will be evaluated using a semi-quantitative score as followed: 0: no change
or minimal changes; 1: decrease size of the calcification less than 50%; 2: decrease of the
calcification between 50 and 90%; 3: more than 90% decrease size or disappearance of the
calcification. Surface of the calcification will be measured on the same view than at
baseline. US of the affected shoulder will be performed as previously described.
