Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05168137 |
| Other study ID # |
MURA2020/762 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2020 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
December 2021 |
| Source |
Mahidol University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In a double-blind, randomized controlled trial, we assigned PLWH receiving ART without a
history of cardiovascular events to received colchicine 0.6 mg once daily or placebo. The
primary endpoint was the mean difference of hs-CRP, IL-6, and IL-1 Ra levels at three and six
months. The secondary endpoint was to access safety outcomes.
Description:
Trial Designs This is a single-center, randomized, double-blind, controlled study comparing
the effect of low-dose colchicine to inflammatory markers at 12-week follow-up with placebo.
The study protocol had been reviewed and approved by the Ethical Committee of Human Rights
Related to Research Involving Human Subjects, Faculty of Medicine Ramathibodi Hospital,
Mahidol University (ethical committee approval number MURA2020/762), and our trial was
conducted following the principles of good clinical practice and the Declaration of Helsinki.
Patient Enrollment PLWH aged more than 30 years old and were receiving
tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), tenofovir/emtricitabine/rilpivirine
(TDF/FTC/RPV), tenofovir/lamivudine/rilpivirine (TDF/3TC/RPV),
tenofovir/lamivudine/dolutegravir (TDF/3TC/DTG) or abacavir/lamivudine/efavirenz
(ABC/3TC/EFV) for at least six months were enrolled. The patients were eligible for study
entry if the hs-CRP level was more than or equal 2 mg/L, the CD4 level was more than or equal
300 cells/mm3, suppressed HIV viral load, estimated glomerular filtration rate (eGFR) above
30 ml/min/1.73 m2, and they were able to follow-up as protocol.
The exclusion criteria were chronic kidney disease stage 4 and 5 (eGFR less than 30
ml/min/1.73 m2), liver cirrhosis (Child-Pugh class B or C), previous evidence of coronary
artery disease, or cerebrovascular event, and indications or contraindications to colchicine.
Patients were excluded during the study if they had a recent infection within one month or at
least grade 3 adverse events or had indication to use other medication interacted with
colchicine.
Study Objectives The primary objective was to compare the mean difference of hs-CRP,
interleukin-6 levels, and interleukin-1 receptor antagonist from baseline to the 12-week and
24-week follow-up between patients receiving low-dose colchicine and placebo. The secondary
objective was to assess safety outcomes of the low-dose colchicine, e.g., myositis,
agranulocytosis, gastrointestinal side effects, infection.
Trial Conduction This study was conducted at Ramathibodi Hospital (Bangkok, Thailand) from
May 2020 to April 2021. Participants were recruited from the outpatient department
(infectious disease clinic) at Ramathibodi Hospital, Bangkok, Thailand. All participants were
evaluated for eligibility before randomization and follow-up. All patients gave written
informed consent before initiation of the protocol.
PLWH were randomly assigned in a 1:1 ratio to received 0.6 mg of colchicine once daily (group
A) or a matching placebo (group B). Randomization was performed in a double-blinded manner
with computer-generated numbers in the block-of-four method. Clinical evaluations were
scheduled at the time of randomization and at 12-week and 24-week follow-up. Patients
received a brief clinical interview and physical examination, measured weight and height,
taken blood sampling for creatinine and eGFR, creatinine kinase, and complete blood count.
The whole blood was centrifuged at 1000 g for 10 minutes, and plasma was collected to be
stored at -80ºC. All follow-up assessments were completed in person, if possible, or by
telephone. The dose of colchicine was reduced to 0.6 mg every other day if patients had
intolerable gastrointestinal side effects.
Plasma hs-CRP levels were measured by means of particle enhanced immunonephelometry (BN
ProSpec System, Siemens Healthineers, Erlangen, Germany). Polystyrene particles coated with
monoclonal antibodies specific to human CRP are aggregated when mixed with samples containing
CRP. These aggregates scatter a beam of light passed through the sample. The intensity of the
scattered light is proportional to the concentration of the relevant protein in the sample. A
typical limit of detection for hs-CRP is 0.175 mg/L for measurements performed using a sample
dilution of 1:20. A coefficient of variation (CV) of 7.6% was observed from ten replicates of
a sample containing 0.41 mg/L of hs-CRP.
Plasma IL-6 concentrations were measured by sandwich principle using a monoclonal IL-6
specific antibody (mouse) labeled with a ruthenium complex and streptavidin-coated
microparticles (Elecsys IL-6, Cobas, Roche, Rotkreuz, Switzerland). Application of a voltage
to the electrode then induces chemiluminescent emission, which is measured by a
photomultiplier. The minimum detection limit of IL-6 was 1.5 pg/mL, and the coefficient of
variances was less than 10%.
We estimated glomerular filtration rate (GFR) from serum creatinine based on the Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
