Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03357588 |
| Other study ID # |
69/2015 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 29, 2015 |
| Est. completion date |
May 2022 |
Study information
| Verified date |
May 2022 |
| Source |
UMC Utrecht |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The ITREMA trial is an open-label randomized controlled trial (RCT) in which HIV-1 infected
patients initiating first-line ART and already on first-line ART will be enrolled. Enrollment
will continue until 600 patients have been randomized. Patients initiating ART will be
randomized after six months of ART and patients already on ART will be randomized at 6 months
after the last viral load measurement. Patients in both arms will receive study visits every
three months for a total follow-up duration of 18 months after randomization to either of two
study arms. The control arm will receive standard of care HIV-1 treatment monitoring during
first-line ART in accordance with South African National Department of Health (NDoH)
guidelines. The intervention arm will receive intensified treatment monitoring during
first-line ART according to the treatment monitoring strategy under investigation.
Description:
This study will enroll adult HIV-1 infected patients who are about to initiate or have
already initiated first-line ART. Patient enrollment and randomization will be performed at
two different time points. Timing and criteria for enrollment and randomization are as
follows:
1. ART naïve patients: Patients are eligible for enrollment initiation of treatment with
first-line ART. Randomization is performed after availability of the first routine viral
load measurement, performed at month 6 of treatment.
2. Patients on ART: Patients are eligible for enrollment after ≥ 1 year of virologically
suppressive first-line ART and only if a last viral load with a result <1000 copies/mL
was performed within the last 6 months. Randomization is performed 6 months after the
last viral load (VL) result.
A total number of 600 patients will be randomized into two trial arms. The trial will be
conducted on-site at one of the clinical facilities of Ndlovu Care Group
(http://www.ndlovucaregroup.co.za/), one of the partners in the project. This facility,
Ndlovu Medical Centre, is situated in the town of Elandsdoorn, Limpopo, South Africa, and
provides medical service to local South African patients who are unable to pay medical
insurance. The Ndlovu Care Group distributes antiretroviral medication in the framework of
the South African Department of Health antiretroviral treatment programme. This clinic is
currently providing ART to >3600 patients. Patients on ART return to the clinic monthly for
collection of medication, pill count and adherence counselling, which allows intensification
of monitoring without substantial change of the infrastructure or frequency of visits.
After randomisation, patients in both study arms will return for study follow-up visits on a
three-monthly basis, at month 9, 12, 15, 18, 21 and 24 after start of ART or after the last
VL measurement. In addition, patients will be called back for additional study visits (max.
2) in case of a detected viral load >1000 copies/ml during any of these visits. All visits in
both arms, including aforementioned additional call back visits will coincide with standard
of care medication collection visits to the clinic. In case of a switch to second-line
therapy, patients in both arms will continue three-monthly follow-up visits in an
observational manner, and guidelines for monitoring of second-line therapy are followed.
Control arm:
300 patients randomly assigned to this arm will be monitored in full concordance with current
South African NDoH guidelines in use at the study site. Viral load measurements will be
performed at month 12 and 24 after start of ART (for newly initiated patients) or at month 12
and 24 after the last viral load measurement (patients already on ART). If a viral load >1000
copies/ml is detected, the patient is called back for counseling for therapy adherence and
repeat viral load measurement, 2 months after the initial viral load measurement. If the
repeat viral load measurement is >1000 copies/ml after adherence counseling, this is taken to
be indicative of therapy failure due to development of drug resistance and a switch to second
line therapy is made, together with intensified adherence counseling, without verifying the
cause of virological failure by performing drug level testing or drug resistance testing. If
viral load drops to <1000 copies/ml after adherence counseling, the first line treatment is
maintained.
Intervention arm:
300 patients randomly assigned to this arm will be monitored using the investigational
intensified monitoring strategy. This strategy consists of 3-monthly viral load monitoring at
month 9, 12, 15, 18, 21 and 24 (after start of ART in initiating patients or after the last
viral load measurement in patients on ART). If a viral load measurement > 1000 copies/mL is
detected, the patient will be called back for a follow-up study visit at the next monthly
medication collection visit (4 weeks after detection of elevated viral load). Upon arrival
drug level testing is performed, the viral load measurement is repeated, and a dried blood
spot prepared and stored at room temperature. Procedures following this depend on the result
of drug level testing:
- If drug levels are detected by drug level testing, the result of the viral load
measurement is awaited. If the repeat viral load is >1000 copies/ml, the dried blood
spot is shipped directly by courier to the World Health Organization (WHO) reference
laboratory for drug resistance testing. The reference laboratory will provide feedback
by means of a digital resistance report to the coordinating research physician. The
patient will be called back for a second follow-up study visit at the next monthly
medication visit (8 weeks after detection of elevated viral load), either for
prescription of second-line therapy or continuation of first-line therapy, guided by the
result of resistance testing.
- If drug level monitoring at the first follow-up visit indicates that drug levels are not
detected, intensified counseling is performed at the same visit and first-line therapy
will be maintained, regardless of the result of the repeat viral load measurement. The
patient will not be called back and the next viral load will be performed at the next
scheduled three-monthly time point. However, if the viral load result at this visit is
again >1000 copies/ml, drug resistance testing will be performed regardless of the
outcome of drug level testing.
