Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02035969 |
| Other study ID # |
K2012-56X-22028-01-3 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 2013 |
| Est. completion date |
January 4, 2022 |
Study information
| Verified date |
February 2021 |
| Source |
Karolinska Institutet |
| Contact |
Mattias Larsson, MD, PhD |
| Phone |
+46707663068 |
| Email |
Mattias.Larsson[@]ki.se |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This project aims to assess the effect of group peer support to children with HIV in relation
to adherence, virological treatment failure as well as physical development. A randomised
controlled trial (RCT) will be used where HIV+ children on antiretroviral treatment (ARV) and
their caretakers are randomized into either enhanced treatment support (ETS) through peer
supporters or the conventional treatment (CT) according to the guidelines of The National
AIDS Control Program. The treatment strategies will be assessed and compared in relation to
virological treatment failure as primary endpoint, immunological and clinical (AIDS events
and mortality) as secondary endpoints as well as treatment adherence and physical
development. The results from this project will lead to an increased knowledge in relation to
the impact of enhanced treatment support on adherence, virological suppression and resistance
development for children with HIV and have an impact on HIV treatment policies and guidelines
for Pediatric HIV in low-income settings globally.
Description:
Main Aim To study the impact of peer support to children with HIV on antiretroviral treatment
(ART) in relation to adherence, virological treatment failure, HIV drug resistance
development as well as physical development using a randomised controlled trial (RCT) design
comparing enhanced treatment support (ETS) and conventional treatment (CT).
Specific Aims
1. To assess the rate and risk factors for virological treatment failure among children on
ART for more than 6 months using HIV viral load in blood in relation to clinical and
socioeconomic indicators.
2. To recruit 520 HIV+ children 0-12 years of age on ART and randomize to either enhanced
treatment support (ETS) or conventional treatment (CT).
3. To monitor ART adherence, CD4+ T-cell count, HIV viral load, clinical status, physical
and cognitive development AIDS-associated events and/or mortality during every 6 months
during a 36 months follow up period.
4. To assess the effect of ETS compared to CT with respect to the primary endpoint,
virological treatment failure and specific ART mutations as well as the secondary
endpoints, immunological failure, ART adherence, physical and cognitive development, and
mortality and/or AIDS events.
5. To conduct a cost effectiveness assessment comparing ETS and CT.
This is a multi center study that includes the National Pediatric Hospital in Hanoi and the
two major pediatric hospitals in Ho Chi Minh City. A study population of 520 HIV+ children
receiving ARTs will be recruited from these hospitals. The reason for selecting children on
ART is to see if treatment support can be initiated successfully after initiation of ART.
Each HIV+ patient is examined according to WHO guidelines. HIV+ children will receive a
complete physical examination including clinical staging of HIV infection, opportunistic
infections and evidence of tuberculosis. Laboratory testing will include full blood count,
CD4+ T-cell count (for children under five years of age CD4 %), viral load using ExaVirR
viral load and liver enzymes. If indicated (e.g. prolonged cough and/or fever) chest X-ray,
sputum microscopy for AFB will be done.
Opportunistic infections in HIV+ patients will be treated according to national guidelines.
HIV+ children and their caregivers receive counselling and clinical follow ups. Tuberculosis
(TB) will be managed in collaboration with the National Tuberculosis Program.
Inclusion and exclusion criteria's are described below. The patients recruited will be
stratified according to age, sex and identified risk factor, then they will be randomised
into two different treatment strategies a) Enhanced treatment support (ETS) strategy
(described below) and Conventional treatment (CT). The patients treated under the two
strategies will be compared with respect to: (i) virological treatment failure, (ii)
patient's adherence to treatment strategy, (iii) physical development, and (iv) mortality and
AIDS event. First drug regimen for all patients includes stavudine or AZT, lamivudine,
nevirapine or efavirens. All procedures, treatment, and follow up for adverse effects are
done according to national guidelines. The health care workers are trained in regular
monitoring of patients and implementation of optimal treatment strategy. All procedures and
treatment will follow the national guidelines. Follow up visits including physical
examinations, adherence evaluation and laboratory tests will be done every 3 months.
The tests will include full blood count and liver enzymes as well as other indicated tests.
Viral load and CD4+ T-cell count will be monitored every 6 months.
The number of patients needed for each arm of the experiment was estimated assuming an
absolute 2-year risk of treatment failure of 15% in the control arm. Assuming proportional
hazards there is an absolute 2-year risk of failure in the peer-support group of 7%.
Requiring a power of 80% and a significance level of 5% approximately 480 patients are
required. In order to account for some losses to follow-up and deviations from our
assumptions, we will recruit a total of 260 patients into each arm.
In the ETC strategy caretakers and children with HIV on ART will be supported to achieve
better adherence through peer support groups at the beginning of treatment and phone
follow-up later, with an option for home visits or to return to support groups later if
necessary. The activities will be organized by peer supporters, caregivers of HIV-infected
children selected by peers, who will undergo a series of training, including medication
adherence and counselling skills. They will ideally be assigned to patients living in the
same community or in proximity to patients in the intervention group.
Peer group meetings with 7-10 caretakers and children will be organized monthly according to
age groups, e.g. 0-3 years, 4-6 years, 7-12 years, and location. In these meetings caretakers
will discuss problems related to adherence and receive new information from peer supporters.
Simultaneously, children above 3 years of age will receive age relevant information about
their disease and treatment from another supporter as well as do games and play to enhance
group bounds. The supporters will also have weekly telephone contact with the caretakers, if
needed more, to assess the condition of the child. To those who cannot make a particular
meeting or answer the phone home visits (if consent is given) are made. Follow up phone calls
will be made to those whom the case manager identifies to need more support.
As children differ very much depending on age the intervention will be adjusted to each age
group in order to provide the best possible support according to standardized procedures that
can be replicated. For children with poor adherence individual support to caretakers and
patients will be arranged where the condition of the child and reason for poor adherence is
assessed, in case of complications the peer supporter will provide advice and if needed refer
the child for medical checkup. In CT control group the treatment will be supported according
to the treatment guidelines. Both groups will receive treatment counseling and be followed
through regular clinical check-up, the drugs will be provided in a pre-packed dosage form for
easy remembering and counting of the pills.
The patients are followed for 36 months and monitored each six months through viral load in
plasma using ExaVir Load®, CD4+ T-cell count, adherence, clinical examination including
physical development. Viral load will be assessed using a new ELISA based technique ExaVir
Load® that detects HIV reverse transcriptase down to 1 fg/ml blood-plasma corresponding to
200 HIV RNA copies/ml. Adherence will be assessed every three months using questionnaires
designed specifically for age groups. For infants and young children the Pediatric
International Adherence Questionnaire (PIAQ) may be used, and for older children the Adult
AIDS Clinical Trials Group (ACTG) Adherence Instruments will be used. The questionnaire
interviews will be conducted by health personnel at the Out Patient Clinics for Pediatric
HIV. Adherence will also be measured by pill count, where the patients bring their remaining
drugs back to the clinic at follow-up, enabling calculation of the proportion of drugs
remaining out of the total amount of prescribed drugs as well as through pharmacy records if
the patients have collected the drugs accurately. Assessment of side effects will be done
according to WHO suggested monitoring and management of ARV drugs together with the clinical
examination each three months.
The primary endpoint will be virological treatment failure defined as a viral load
corresponding to 1000 copies/ml. This could also be expressed as loss of virological response
taking death and Loss of Follow Up into account. The secondary endpoints immunological
treatment failure (no rise in CD4+ T-cell count at 1 year or decrease with 50% compared to
the highest value or CD4+ T-cell count below 100), clinical treatment failure as defined by a
new AIDS-defining illness or death due to HIV/AIDS (including TB and opportunistic infection)
after starting treatment, and physiological development.
Costing of the two different strategies will be carried out by collecting monetary data of
expense for drugs, test, allowance and other expenses from perspective of the HIV/AIDS
treatment provider during ART. The investigators follow the basic principles of
activity-based costing by identifying all activites necessary to provide the ETS and CT and
then calculate the costs of carrying out each activity. Costs for each activity comprise
recurrent and capital costs, direct and indirect costs. Recurrent costs are the routine costs
of resources that are consumed within a year, i.e., non-capital items such as labor and
medical supplies. Capital costs represent the annual portion of the cost of durable HIV Sida
DOTARV assets. Effectiveness will be measured by percentages of patients with virological
treatment failure defined as Viral Load >400 copise/ml.
The statistical analysis mainly consists in the comparison between the two groups with
respect to the defined primary and secondary endpoints in relation to the semi-quantitative
assessments of adherence. Standard statistical methods will be used. Hazard/Survival analysis
will be conducted including death/loss of follow up as 'failure' in the analysis. Intention
to treat will be used for analysis. Regression models with outcome as the dependent variable
and a group indicator together with patient characteristics as independent variables will be
the main approach. For binary outcomes, logistic regression will be used. Attention has to be
paid to the particular, often skewed, distributions of variables like CD4+ T-cell counts and
viral load. Transformations or the use of non-parametric approaches are likely to be
necessary if such measures are not dichotomized and used in linear regression. The
correlation between drug resistance and adherence will be statistically analyzed in order to
study whether the basic mechanisms of selective drug pressure result in a concave or
bell-shaped resistance - adherence relationship, for these drugs during ETS or CT in a
low-income setting. The odds ratios of having or not baseline drug resistance mutations as
detected by population and deep (single allele PCR) sequencing on drug resistance development
and clinical outcomes during treatment independent of treatment adherence will be evaluated.
Stratified analysis will be conducted comparing the outcomes among the treatment groups.
The investigators will strictly comply with widely recognized international texts and codes
of practice including the Helsinki agreement. In this project one patient cohort will receive
ETS and the other CT. However both groups will be encouraged to proceed regularly with their
drug treatment and to present difficulties that they may encounter in doing so. For the
project period, the project will meet the costs of ART for the cohorts. Patients' biological
samples will be collected and used only after written consent from the children's caretaker.
All specimens will be coded to protect the identity of patients and to ensure
confidentiality. Patients will be recruited in a consecutive manner without regard to race or
other exclusion considerations. Confidentiality will be assured by using codes for patient
identification, and confidentially laws will be strictly observed when processing human
clinical information. No patient identifying information will be published or available after
the requisite clinical data has been collected, and consent will be obtained for the use of
all data and tissues. Data will be accessible only to members and coordinators of the tissue
procurement facility and research team, under approved guidelines.
