Clinical trial NCT00301561: Antiretroviral Treatment Simplified Follow-up Management Assessment (ANRS 12110 STRATALL)
Official title: Expanded Access to Antiretroviral Therapy in Africa: Assessment of the Patients' Management in District Hospitals With a Simplified Follow-up Approach (ANRS 12110 STRATALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
AIDS
Keywords: Antiretroviral treatment
Expanded access
Africa
Treatment Naive
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2006-03-13
Enrollment: 459
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Access to antiretroviral therapy (ART) is still limited in Africa (11% of patients in immediate need in June 2005). Face to the scope of the need and the constraints (unavailability and cost of viral load and CD4 cell count, lack of physicians...), WHO has developed a follow-up approach based on a simplified monitoring. However, this "simplified" approach which represents a major stake for the expanded access to ART has been little evaluated against the gold standard approach.

Detailed description: Justification

Access to antiretroviral therapy (ART) is still limited in Africa (11% of patients in immediate need in June 2005). Face to the scope of the need and the constraints (unavailability and cost of viral load and CD4 cell count, lack of physicians...), WHO has developed a follow-up approach based on a simplified monitoring. This "simplified" approach restricting the use of complementary exams including biologic criteria of effectiveness and tolerability, some people consider this approach as dangerous for the patient but also for the community (rapid emergence of resistances) and that it would be preferable to treat less patients and only with the gold standard approach. In practice, this "simplified" approach which represents a major stake for the expanded access to ART has been little evaluated against the gold standard approach.

Objectives

Main objective: To compare the increase in the CD4 cell count in patients receiving ART with a "simplified" approach and in those treated with the gold standard approach in district hospitals.

Secondary objectives: To compare between the two approaches the virologic effectiveness, survival, treatment interruptions, number of patients lost to follow-up, clinical progression, clinical and biologic tolerability, adherence, emergence of drug resistances, impact on patients' daily life, acceptability by the patients and health professionals, and cost-effectiveness performances.

Methods

Randomised, controlled, multicentre, non inferiority, intervention trial, without blind for approach, in 9 district hospitals of the Province du Centre in Cameroon. 430 adult patients will be randomised in two groups ("simplified" approach or gold standard approach) with a 1:1 ratio and followed for 24 months.

In the "simplified" approach, the results of the HIV-1 viral load and CD4 cell count will not be available for the management of patients, the biologic assessment of tolerability will be limited and some clinical consultations will be performed by nurses under the physicians' responsibility; the remainder will be similar to the gold standard approach.

Planning

The study will start in the first semester of 2006. The full length of the study would be 36 months maximum (12 months for enrolment and 24 months for follow-up).

Expected results

Advices for increasing access to ART in Africa.

Eligibility criteria: Inclusion Criteria:

* Men or women aged at least 18 years
* Living in the health district of the hospital attended
* Confirmed HIV-1 group M infection
* Meeting one of the following criteria:

  * Stage III or IV (WHO classification)
  * Stage II (WHO classification) and total lymphocytes count ≤ 1200/mm3
* Patient agreeing on monthly follow-up and treatment for 24 months
* Signed informed consent

Exclusion Criteria:

* HIV-1 group O or N, or HIV-2 infection
* HIV-1 primary infection
* Progressive tuberculosis in treatment and total lymphocytes count \> 1200/mm3
* Progressive tumor or malignant lymphoma (except cutaneous or mucous Kaposi sarcoma)
* Progressive psychiatric disorder
* Hepatocellular disorder
* History of antiretroviral therapy
* Pregnancy

Primary outcomes:
measure: Increase in the CD4 cell count measured with a FACSCount apparatus after 24 months of antiretroviral therapy
timeFrame: 24 months
Secondary outcomes:
measure: Percentage of patients with viral load below 400 copies/ml and 50 copies/ml, respectively (Abbott RealTime HIV-1)
timeFrame: 12 and 24 months
measure: Survival probability
timeFrame: Through out the trial
measure: Probability of treatment interruption
timeFrame: Through out the trial
measure: Probability of patients lost to follow-up
timeFrame: Through out the trial
measure: Incidence of side effects
timeFrame: Through out the trial
measure: Incidence of clinical events (WHO stage III or IV)
timeFrame: Through out the trial
measure: Percentage of adherence
timeFrame: 12 and 24 months
measure: Percentage of patients with drug resistance
timeFrame: 12 and 24 months
measure: Acceptability by the patients and health professionals of both approaches
timeFrame: 12 and 24 months
measure: Impact on patients' daily life
timeFrame: Through out the trial
measure: Cost-effectiveness ratio
timeFrame: 24 months
Other outcomes:
Locations:
city: Ayos
country: Cameroon
facility: Hôpital de district d'Ayos
city: Bafia
country: Cameroon
facility: Hôpital de district de Bafia
city: Mfou
country: Cameroon
facility: Hôpital de district de Mfou
city: Monatélé
country: Cameroon
facility: Hôpital de district de Monatélé
city: Naga Eboko
country: Cameroon
facility: Hôpital de district de Nanga Eboko
city: Ndikiniméki
country: Cameroon
facility: Hôpital de district de Ndikiniméki
city: Obala
country: Cameroon
facility: Hôpital de district d'Obala
city: Sa'a
country: Cameroon
facility: Hôpital de district de Sa'a
city: Yaounde
country: Cameroon
facility: Hôpital de district de Mbalmayo
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Christian Laurent
role: STUDY_CHAIR
affiliation: Institut de Recherche pour le Developpement
name: Eric Delaporte
role: STUDY_CHAIR
affiliation: Hôpital Central, Yaoundé, Cameroun
name: Sinata Koulla-Shiro
role: STUDY_CHAIR
affiliation: Hôpital Central, Yaoundé, Cameroun
name: Charles Kouandack
role: STUDY_CHAIR
References:
citation: Sandie AB, Molinari N, Wanjoya A, Kouanfack C, Laurent C, Tchatchueng-Mbougua JB. Non-inferiority test for a continuous variable with a flexible margin in an active controlled trial: an application to the "Stratall ANRS 12110 / ESTHER" trial. Trials. 2022 Mar 5;23(1):202. doi: 10.1186/s13063-022-06118-x.
citation: Laurent C, Kouanfack C, Laborde-Balen G, Aghokeng AF, Mbougua JB, Boyer S, Carrieri MP, Mben JM, Dontsop M, Kaze S, Molinari N, Bourgeois A, Mpoudi-Ngole E, Spire B, Koulla-Shiro S, Delaporte E; Stratall ANRS 12110/ESTHER study group. Monitoring of HIV viral loads, CD4 cell counts, and clinical assessments versus clinical monitoring alone for antiretroviral therapy in rural district hospitals in Cameroon (Stratall ANRS 12110/ESTHER): a randomised non-inferiority trial. Lancet Infect Dis. 2011 Nov;11(11):825-33. doi: 10.1016/S1473-3099(11)70168-2. Epub 2011 Aug 8.