|- candidate number||1798|
|- NTR Number||NTR474|
|- Date ISRCTN created||19-apr-2005|
|- date ISRCTN requested|
|- Date Registered NTR||31-okt-2005|
|- Secondary IDs||N/A |
|- Public Title||The Delphi Trial - I(RCT)˛.
|- Scientific Title||The Delphi Trial - I(RCT)˛.
International Randomized Clinical Trial of Rheumatoid Craniocervical Treatment.
An Intervention-Prognostic Trial comparing ‘early’ surgery with natural history.|
|- ACRONYM||The Delphi Trial - I(RCT)˛|
|- hypothesis||1. Is an early surgery treatment strategy in neurological intact patients, with rheumatoid arthritis and radiological signs of craniocervical pathology, (cost-) effective when compared to prolonged conservative treatment?
What is the time-dependant Hazard-Ratio of the surgical group compared to the conservative treatment group? Hazard is defined as severe neurological deficit or death.
During the explorative analyses the next questions will be answered.
2. Is it possible to define subgroups, which benefit most from one of the allocated treatment strategies?
3. Does the type of C1C2 fixation influence the fusion rate and result in the surgical group?|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis|
|- Inclusion criteria||1. Rheumatoid Arthritis patients, seropositive;
2. Age 18-70;
3. Ranawat I and II: no neurological impairment;
4. C1-C2 subluxation: AADI: 5-12 mm;
5. C1-C2 subluxation reducible or irreducible;
6. Informed consent.|
|- Exclusion criteria||1. Ranawat IIIA and IIIB: neurological impairment;
2. Severe comorbidity;
3. Previous craniocervical operations;
4. C1-C2 subluxation: AADI < 5 or 8 mm or > 12 mm or PADI < 10 mm;
5. MRI incompatibility.|
|- mec approval received||yes|
|- multicenter trial||yes|
|- planned startdate ||1-okt-2005|
|- planned closingdate||1-okt-2017|
|- Target number of participants||250|
|- Interventions||Surgical treatment: Different surgical opportunities and techniques for cervical fixation exist. The choice of technique depends on the severity of the cervical spine involvement and the surgeon’s preference. Surgery will be performed according to local standards and to the discretion of the surgeons, but a standardized minimal surgical technique is required. All approved cervical spine fixation systems are allowed in this trial. If AAS is present a C1-C2 screw fixation according to Magerl or Harms with or without wiring techniques, or a Hook C1-C2 fixation will be performed. When vertical translocation has occurred, the cranium will be fixated to the upper cervical spine with fixation to the C1-C2 screws. For each patient, the surgeons will register which technique they have used.
Conservative treatment: Conservative treatment consists of antirheumatoid drugs (i.e., NSAID, DMARD). The choice of drugs is to the discretion of the rheumatologist. Occurrence of progressive neurological deficit, progressive radiological abnormalities, and intolerable pain represent a failure of conservative management and are an indication for surgical fixation. |
|- Primary outcome||The primary outcome is the occurrence of a major event:
1. Neurological disability (paraesthesias, worsened Myelopathy Disability Index > 3 points);
2. Radiological progression (signs of myelopathy on MRI, impression of brainstem by vertical translocation, AADI > 12 mm, Vertical translocation);
3. Surgery (B) or resurgery (A) in case of progression to a stadium that longer wait and see will result in inevitable neurological deficit or death;
4. Death (all causes).|
|- Secondary outcome||Secondary outcome measures are Ranawat, ASIA, DAS-28, VAS, EuroQol, SF-36, functional X-ray and MRI. The outcome will be evaluated at fixed intervals and a Kaplan Meier Survival Analysis will be performed. |
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Drs. J.F.C. Wolfs|
|- CONTACT for SCIENTIFIC QUERIES||Drs. J.F.C. Wolfs|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC), Department of Neurosurgery|
(Source(s) of Monetary or Material Support)
|Dutch Arthritis Association (Reumafonds), Leiden University Medical Center (LUMC), Cervical Spine Research Society (CSRS)|
|- Brief summary||Rheumatoid arthritis is a chronic inflammatory disease, which affects 1% of the population (1). Hands and feet are most commonly involved in the disease followed by the cervical spine (17-86%) (2). The spinal column consists of vertebrae stabilized by an intricate network of ligaments. Especially in the cervical spine, rheumatoid arthritis can cause degeneration of these ligaments, causing laxity, instability and subluxation of the vertebral bodies. Subsequent compression of the spinal cord and medulla oblongata can cause severe neurological deficits and even sudden death. Once neurological deficits occur, progression is inevitable although the rapidity of progression is highly variable (1). The first signs and symptoms are pain at the back of the head caused by compression of the major occipital nerve, followed by loss of strength of arms and legs. The degree of subluxation can be observed with radiological investigations (MRI, CT) with a high sensitivity. In order to prevent progression of neurological impairments, surgery can be performed aiming at fixation of the first and second vertebrae, sometimes in combination with the occiput.
There is an ongoing international discussion about the best timing of surgery, because of the unknown rate of progression of the subluxation and neurological deficits. In some countries patients are operated on in an early stage of the disease when no neurological impairments have occurred yet. In the Netherlands and United Kingdom the current policy is to operate after the onset of neurological signs and symptoms. If myelopathic deficits are present there is little chance of recovery to normal levels after surgery. Early surgery has peri-operative morbidity and causes loss of rotation of the head and neck.
In this multicenter study we want to analyze which strategy of treatment has the best outcome. There will be two groups: 1. early surgery without neurological complaints but with radiological evidence of cervical spine involvement, and 2. a 'wait and see' policy. The hypothesis is that with early surgery progression of the disease within the cervical spine can be prevented and people will remain ambulant for an extended period. By randomizing this multicenter international study we will analyze which of the two strategies of treatment is the optional one with respect to the functional neurological outcome. |
|- Main changes (audit trail)|
|- RECORD||31-okt-2005 - 6-mrt-2006|