A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure

NCT ID: NCT01641367

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 545 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-22
• Study Completion Date: 2018-12-31

Brief Summary

The study was done to:

• test a strategy of using a resistance test to choose anti-HIV drugs
• see how well combinations of new anti-HIV drugs work to lower HIV infection
• see if taking new anti-HIV drugs together is safe and tolerable
• see if text messages improve people's anti-HIV drug-taking behavior (only at sites participating in the adherence study)
• in people taking certain combinations of anti-HIV drugs with an anti-TB drug, compare how these drugs act in the body
• to see how people do after they stop having frequent clinic visits as part of a research study

Detailed Description

A5288 was an open-label phase IV, prospective interventional, strategy study in resource-limited settings (RLS) for HIV-1 infected participants with triple-class experience or resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors (PIs) and who were failing their current regimen. The use of novel agents and contemporary clinical decision management tools that include standard genotyping and plasma HIV viral load (VL) monitoring were evaluated. The screening genotype results and antiretroviral (ARV) history were used to allocate potential participants to one of four Cohorts (A, B, C or D) and to select an associated ARV regimen based on the Cohort assignment. In brief, individuals assigned to Cohort A continued on the same PI as in their second-line regimen, with the ability to modify NRTIs. Those assigned to Cohort B who were negative for hepatitis B were randomized to receive RAL and DRV/RTV with either the best available NRTIs (Cohort B1) or ETR (Cohort B2). If they were positive for hepatitis B they were assigned to Cohort B3 and received RAL, DRV/RTV and either FTC/TDF or 3TC/TDF. Individuals assigned to Cohort C received RAL and DRV/RTV with the best available NRTIs. Those ineligible for Cohorts A, B or C were assigned to Cohort D and received the best available regimen that included study provided drugs and any locally provided drugs.

At sites where feasible and relevant, the study evaluated an adherence support intervention. This involved a randomized comparison of a cell phone-based adherence support intervention plus local standard-of-care adherence support procedures (CPI+SOC) versus the SOC adherence support procedures.

Participants enrolled to the study in Step 1. If a participant experienced a confirmed virologic failure (defined as two consecutive HIV-1 RNA measures >= 1000 copies/mL) at/after 22 weeks on their Step 1 regimen, they had another genotype test performed and cohort/regimen selected for Step 2. With the exception of one additional visit 4 weeks after enrollment to Step 2, the visit schedule for Step 2 followed the participant's original Step 1 schedule throughout the remainder of follow up.

Participants were followed in Steps 1 and 2 until 48 weeks after the last participant was enrolled to Step 1. During the first 48 weeks after Step 1 enrollment, clinic visits occurred at weeks 4, 12, 24, 36 and 48. After week 48, visits occurred every 12 weeks for adherence, safety and efficacy measures.

Participants had a final step 1/2 visit between November 22, 2016 and February 13, 2017. At the final step 1/2 visit, participants taking RAL, ETR, or DRV who were unable to obtain these drugs locally (e.g., through local treatment programs), and were otherwise eligible, entered Step 3 and continued to receive these drugs through the study for up to 96 additional weeks. Step 3 participants were dispensed ARVs every 12 weeks and had clinical assessments every 24 weeks. The purpose of Step 3 was to assist participants with the transition back to local care.

The primary analysis specified in the protocol and in the Statistical Analysis Plan was to estimate the proportion of participants in the overall study population who were virologically suppressed (HIV-1 RNA ≤200 copies/mL) at week 48 with a 95% confidence interval.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Group Type: EXPERIMENTAL

Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs)

Intervention Type: DRUG

LPV/r and ATV/r were the preferred bPIs for second-line ART. TDF + (3TC or FTC) or AZT + 3TC were the most frequent NRTI backbones. Cohort A did not include any of the new drugs; therefore, it is distinct from Cohorts B, C, and D.

SOC adherence versus SOC+CPI adherence

Intervention Type: OTHER

• not participating in the adherence randomization; OR
• randomized to SOC adherence; OR
• randomized to SOC+CPI adherence.

Sub-cohort B1

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening

• Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day \[200 mg per day\])

Raltegravir

Intervention Type: DRUG

Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food

SOC adherence versus SOC+CPI adherence

Intervention Type: OTHER

• not participating in the adherence randomization; OR
• randomized to SOC adherence; OR
• randomized to SOC+CPI adherence.

Sub-cohort B2

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening

• ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day \[200 mg per day\])

Etravirine

Intervention Type: DRUG

Patients were administered Etravirine orally as two 100 mg tablets or one 200 mg tablet twice a day (400 mg per day) following a meal.

Raltegravir

Intervention Type: DRUG

Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food

SOC adherence versus SOC+CPI adherence

Intervention Type: OTHER

• not participating in the adherence randomization; OR
• randomized to SOC adherence; OR
• randomized to SOC+CPI adherence.

Sub-cohort B3

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day \[200 mg per day\])

Emtricitabine/tenofovir disoproxil fumarate

Intervention Type: DRUG

Patients were administered FTC/TDF orally as one fixed dose combination tablet (FTC 200 mg/TDF 300 mg) once daily, with or without food.

Raltegravir

Intervention Type: DRUG

Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food

SOC adherence versus SOC+CPI adherence

Intervention Type: OTHER

• not participating in the adherence randomization; OR
• randomized to SOC adherence; OR
• randomized to SOC+CPI adherence.

Cohort C

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV)

• Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Group Type: EXPERIMENTAL

Darunavir

Intervention Type: DRUG

Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day \[200 mg per day\])

Raltegravir

Intervention Type: DRUG

Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food

SOC adherence versus SOC+CPI adherence

Intervention Type: OTHER

• not participating in the adherence randomization; OR
• randomized to SOC adherence; OR
• randomized to SOC+CPI adherence.

Cohort D

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs

Group Type: EXPERIMENTAL

Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available

Intervention Type: DRUG

For Cohort D, in many situations a participant received the same regimen that patients are getting in Cohorts B and C if that was the best combination that can be obtained according to his/her resistance profile and drug availability (as for many countries there were no further drug options beyond the available study drugs).

SOC adherence versus SOC+CPI adherence

Intervention Type: OTHER

• not participating in the adherence randomization; OR
• randomized to SOC adherence; OR
• randomized to SOC+CPI adherence.

Interventions

Darunavir

Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day \[200 mg per day\])

Intervention Type: DRUG

Etravirine

Patients were administered Etravirine orally as two 100 mg tablets or one 200 mg tablet twice a day (400 mg per day) following a meal.

Intervention Type: DRUG

Emtricitabine/tenofovir disoproxil fumarate

Patients were administered FTC/TDF orally as one fixed dose combination tablet (FTC 200 mg/TDF 300 mg) once daily, with or without food.

Intervention Type: DRUG

Raltegravir

Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food

Intervention Type: DRUG

Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs)

LPV/r and ATV/r were the preferred bPIs for second-line ART. TDF + (3TC or FTC) or AZT + 3TC were the most frequent NRTI backbones. Cohort A did not include any of the new drugs; therefore, it is distinct from Cohorts B, C, and D.

Intervention Type: DRUG

Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available

For Cohort D, in many situations a participant received the same regimen that patients are getting in Cohorts B and C if that was the best combination that can be obtained according to his/her resistance profile and drug availability (as for many countries there were no further drug options beyond the available study drugs).

Intervention Type: DRUG

SOC adherence versus SOC+CPI adherence

• not participating in the adherence randomization; OR
• randomized to SOC adherence; OR
• randomized to SOC+CPI adherence.

Intervention Type: OTHER

Other Intervention Names

DRV; Prezista; ETR; Intelence; FTC/TDF; Truvada; RAL; Isentress

Eligibility Criteria

Inclusion Criteria

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
• Any previous combination of ARV treatment at any time with at least one regimen that contained one NNRTI and two NRTIs which was replaced with a PI-based regimen because of virologic, immunologic, or clinical treatment failure, or because of toxicity.

NOTE: All potential participants with prior RAL exposure were assigned to either Cohort A or Cohort D.

• At screening, receipt of a PI-based regimen with no regimen change for a minimum of 24 weeks prior to screening.
• Confirmation of VF of current second-line PI-based ART. NOTE A: Failure of the current second-line regimen was defined as two consecutive measurements of plasma HIV-1 RNA ≥1000 copies/mL obtained at least 1 day apart while on the current PI-based regimen. "Current PI-based regimen" and "current regimen" were understood to be the regimen described (ie, the regimen that the candidate was taking when the first VF sample was drawn plus only those modifications allowed).
• CD4+ T-cell count result from a specimen drawn within 103 days prior to study entry
• Laboratory values obtained within 30 days prior to study entry:

• Absolute neutrophil count (ANC) ≥ 500/mm^3
• Hemoglobin ≥7.5 g/dL
• Platelet count ≥40,000/mm^3
• Creatinine ≤2 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase ≤5 x ULN
• Total bilirubin ≤2.5 x ULN
• Creatinine clearance (CrCl) >30 mL/min, either measured or estimated by Cockcroft-Gault equation
• Hepatitis B panel that includes HbsAB, HBcAB, and HBsAG or only HBsAG, with plasma stored for later anti-HBs and anti-HBc.

NOTE A: Candidates who were eligible for cohort B and who were positive for active hepatitis B infection were assigned to sub-cohort B3 at registration/randomization.

NOTE B: Candidates with CrCl <60 mL/min who were also positive for active hepatitis B infection were not eligible.

• Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, hysterectomy or bilateral salpingectomy or bilateral oophorectomy or tubal ligation) must have had a negative serum or urine pregnancy test prior to the submission of the screening genotype testing sample and again within 48 hours prior to randomization or registration.
• Female participants of reproductive potential must have agreed not to participate in the conception process (ie, active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female participant must have used at least one reliable form of contraceptive. Female participants must have continued to use contraceptives while receiving study treatment and for 6 weeks after stopping study treatment.

Acceptable forms of contraceptives included:

• Condoms (male or female) with or without a spermicidal agent
• Diaphragm or cervical cap with spermicide
• Intrauterine device (IUD)
• Hormonal contraception

Female participants who were not of reproductive potential or whose male partner(s) had documented azoospermia) were not required to use contraceptives. Any statement of self-reported sterility or that of her partner's must have been entered in the source documents.

NOTE: Acceptable documentation of lack of reproductive potential was oral or written documentation from the participant.

• Karnofsky performance score >/= 70 within 30 days prior to study entry.
• Ability and willingness of potential participant to provide informed consent.
• Willingness of potential participant to adhere to protocol requirements, especially with respect to treatment assignment and ability to obtain non-study provided ART, if needed.
• Ability to take oral study medications.
• No intention of permanent relocation that would preclude attending Step 1 and 2 study follow-up visits.
• Availability of a successful, interpretable resistance genotype report from a DAIDS-approved regional genotyping facility from testing performed on a plasma sample that was collected during screening (ie, at or after the date that a sample is collected to confirm HIV-1 virologic failure) and which was shipped to a regional resistance testing laboratory once documentation of two screening plasma HIV-1 RNA values ≥1000 copies/mL were available.
• Identification of a cohort assignment and ARV regimen for use on study, selected from the recommended options provided by the site investigator, and reviewed and approved by the A5288 Clinical Management Committee (CMC).

Exclusion Criteria

• Pregnancy or breast-feeding.
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would have interfered with adherence to study requirements.
• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or was clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.
• Concurrent illness or condition that would compromise the ability to take study medication, follow the protocol, or that would make participation not in the best interest of the participant, per the site investigator.
• Requirement for taking any of the prohibited medications with the selected ARV study regimen, or within 14 days prior to study entry.

NOTE: Study candidates should not have discontinued any component of their ART during screening. The 14-day restriction on prohibited medications did not apply to ARVs.

• Active tuberculosis (TB) or rifampin exposure less than 2 weeks prior to study entry.
• Any exposure to darunavir or etravirine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Janssen Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Dimagi Inc.

INDUSTRY

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Beatriz Grinsztejn, MD, PhD

Role: STUDY_CHAIR

Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz

Peter Mugyenyi, MB ChB, FRCP, DSc

Role: STUDY_CHAIR

Joint Clinical Research Center

Locations

Hospital Nossa Senhora da Conceicao CRS (12201)

Porto Alegre, Rio Grande do Sul, Brazil

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, , Brazil

Les Centres GHESKIO CRS (30022)

Port-au-Prince, Bicentaire, Haiti

GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS

Port-au-Prince, , Haiti

BJ Medical College CRS (31441)

Pune, Maharashtra, India

Chennai Antiviral Research and Treatment (CART) CRS (11701)

Chennai, Taramani, India

AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)

Eldoret, , Kenya

Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) CRS (31460)

Kisumu, , Kenya

Malawi CRS (12001)

Lilongwe, , Malawi

San Miguel CRS (11302)

San Miguel, Lima region, Peru

Barranco CRS (11301)

Lima, , Peru

University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101)

Johannesburg, Gauteng, South Africa

Family Clinical Research Unit (FAM-CUR) CRS (8950)

Cape Town, West Cape, South Africa

Durban Adult HIV CRS (11201)

Durban, , South Africa

Soweto ACTG CRS (12301)

Johannesburg, , South Africa

31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS

Bangkok, Patumwan, Thailand

31784 Chiang Mai University HIV Treatment CRS

Chiang Mai, , Thailand

JCRC CRS

Kampala, , Uganda

UZ-Parirenyatwa CRS (30313)

Harare, , Zimbabwe

Countries

Brazil; Haiti; India; Kenya; Malawi; Peru; South Africa; Thailand; Uganda; Zimbabwe

References

Avihingsanon A, Hughes MD, Salata R, Godfrey C, McCarthy C, Mugyenyi P, Hogg E, Gross R, Cardoso SW, Bukuru A, Makanga M, Badal-Aesen S, Mave V, Ndege BW, Fontain SN, Samaneka W, Secours R, Van Schalkwyk M, Mngqibisa R, Mohapi L, Valencia J, Sugandhavesa P, Montalban E, Munyanga C, Chagomerana M, Santos BR, Kumarasamy N, Kanyama C, Schooley RT, Mellors JW, Wallis CL, Collier AC, Grinsztejn B; A5288 Study team. Third-line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource-limited settings: ACTG A5288 strategy trial. J Int AIDS Soc. 2022 Jun;25(6):e25905. doi: 10.1002/jia2.25905.

Reference Type: DERIVED

PMID: 36039892 (View on PubMed)

Godfrey C, Hughes MD, Ritz J, Coelho L, Gross R, Salata R, Mngqibisa R, Wallis CL, Mumbi ME, Matoga M, Poongulali S, Van Schalkwyk M, Hogg E, Fletcher CV, Grinsztejn B, Collier AC; A5288 team. Brief Report: Sex Differences in Outcomes for Individuals Presenting for Third-Line Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2020 Jun 1;84(2):203-207. doi: 10.1097/QAI.0000000000002324.

Reference Type: DERIVED

PMID: 32049773 (View on PubMed)

Gross R, Ritz J, Hughes MD, Salata R, Mugyenyi P, Hogg E, Wieclaw L, Godfrey C, Wallis CL, Mellors JW, Mudhune VO, Badal-Faesen S, Grinsztejn B, Collier AC. Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomised controlled trial. Lancet Digit Health. 2019 May;1(1):e26-e34. doi: 10.1016/S2589-7500(19)30006-8. Epub 2019 May 6.

Reference Type: DERIVED

PMID: 31528850 (View on PubMed)

Grinsztejn B, Hughes MD, Ritz J, Salata R, Mugyenyi P, Hogg E, Wieclaw L, Gross R, Godfrey C, Cardoso SW, Bukuru A, Makanga M, Faesen S, Mave V, Wangari Ndege B, Nerette Fontain S, Samaneka W, Secours R, van Schalkwyk M, Mngqibisa R, Mohapi L, Valencia J, Sugandhavesa P, Montalban E, Avihingsanon A, Santos BR, Kumarasamy N, Kanyama C, Schooley RT, Mellors JW, Wallis CL, Collier AC; A5288 Team. Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): a prospective strategy study. Lancet HIV. 2019 Sep;6(9):e588-e600. doi: 10.1016/S2352-3018(19)30146-8. Epub 2019 Jul 29.

Reference Type: DERIVED

PMID: 31371262 (View on PubMed)

Related Links

https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf?sfvrsn=6

DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004; Clarification, August 2009

https://rsc.tech-res.com/docs/default-source/safety/manual_for_expedited_reporting_aes_to_daids_v2.pdf?sfvrsn=10

Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Other Identifiers

1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5288

Identifier Type: -

Identifier Source: org_study_id