Safety of Cotrimoxazole in HIV- and HAART-exposed Infants

This study has been completed.
Sponsor:
Collaborators:
Harvard Initiative for Global Health
The American Society of Tropical Medicine and Hygiene
Information provided by:
Harvard School of Public Health
ClinicalTrials.gov Identifier:
NCT01086878
First received: March 12, 2010
Last updated: February 24, 2011
Last verified: February 2011
  Purpose

The purpose of this study is to determine if prophylactic cotrimoxazole makes severe anemia or neutropenia more common in infants exposed to maternal HIV and combination antiretroviral therapy.


Condition Intervention Phase
Acquired Immunodeficiency Syndrome
Infant, Newborn
Anemia
Neutropenia
HIV Infections
Drug: cotrimoxazole
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Safety of Cotrimoxazole in HIV- and HAART-exposed Infants in Botswana

Resource links provided by NLM:


Further study details as provided by Harvard School of Public Health:

Primary Outcome Measures:
  • incidence of severe or life-threatening anemia [ Time Frame: between 1 to 6 months of life ] [ Designated as safety issue: Yes ]
    incidence of severe or life-threatening anemia (as defined by DAIDS toxicity tables, 2004) between 1 and 6 month of life


Secondary Outcome Measures:
  • incidence of severe or life-threatening neutropenia [ Time Frame: between 1 to 6 months of life ] [ Designated as safety issue: Yes ]
    incidence of severe or life-threatening neutropenia (as defined by DAIDS toxicity tables, 2004) between 1 and 6 month of life

  • composite severe morbidity and mortality [ Time Frame: between 1 and 6 months of life ] [ Designated as safety issue: Yes ]
    Composite of severe morbidity (grade 3 or 4 illnesses, DAIDS toxicity tables, 2004), hospitalization, and mortality.


Estimated Enrollment: 222
Study Start Date: February 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cotrimoxazole Drug: cotrimoxazole

Daily oral cotrimoxazole suspension from 1 to 6 months of age at the following weight-based doses:

  • less than 5kg: 100mg sulfamethoxazole, 20mg trimethoprim
  • greater than 5kg: 200mg sulfamethoxazole, 40mg trimethoprim
Other Names:
  • Bactrim
  • Septrim
  • Cotrim
  • Septra
  • trimethoprim/sulfamethoxazole
  • trimethoprim-sulfamethoxazole

Detailed Description:

Each year, more than 2 million children are born to HIV-infected women. The World Health Organization (WHO) recommends that these infants receive cotrimoxazole (CTX) prophylaxis starting at 4-6 weeks of age until the period of infant HIV transmission risk is over, and the infant is known to be HIV-uninfected. There is also increasing interest in studying CTX prophylaxis given to all infants of HIV-infected women at the time of initiation of replacement feeding, regardless of infant HIV infection status, to mitigate the high risk of infant morbidity and mortality associated with formula feeding in the developing world. However, infant in utero exposure to maternal antiretroviral drugs can lead to hematologic toxicities in infants. It is critical to know whether infant CTX prophylaxis exacerbates the hematologic toxicity associated with perinatal ARV exposure. This question, with broad public health implications, has never been studied.

We will study the hematologic toxicity associated with CTX prophylaxis given to infants exposed to maternal HAART in Botswana. We will use existing data from a large cohort that did not receive CTX, and enroll a smaller cohort that does receive CTX according to Botswana national guidelines.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Both maternal and infant criteria need to be met:

Maternal Inclusion Criteria:

  • documented HIV infection
  • taking 3-drug highly active antiretroviral therapy at any point during pregnancy (note: can include 2 NRTI+NNRTI, 2NRTI+PI, or 3 NRTI)
  • 21 years of age or older, and able and willing to sign informed consent
  • Proof of Botswana Citizenship

Maternal Exclusion Criteria:

  • involuntary incarceration

Infant Inclusion Criteria:

  • younger than 42 days of age
  • able to be brought to regular visits at study clinic until at least 6 months postpartum

Infant Exclusion Criteria:

  • known pre-existing birth anomalies resulting in a high probability that the baby will not survive to 6 months
  • known hypersensitivity to cotrimoxazole
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01086878

Locations
Botswana
Scottish Livingstone Hospital
Molepolole, Kweneng, Botswana
Princess Marina Hospital
Gaborone, Botswana
Sponsors and Collaborators
Harvard School of Public Health
Harvard Initiative for Global Health
The American Society of Tropical Medicine and Hygiene
Investigators
Principal Investigator: Shahin Lockman, MD Harvard School of Public Health
  More Information

No publications provided by Harvard School of Public Health

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shahin Lockman, MD, Harvard School of Public Health
ClinicalTrials.gov Identifier: NCT01086878     History of Changes
Other Study ID Numbers: BHP031, 2P30AI060354-06, 3R24TW007988-01S1
Study First Received: March 12, 2010
Last Updated: February 24, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board
Botswana: Health Research and Development Committee
Botswana: Ministry of Health

Keywords provided by Harvard School of Public Health:
Antiretroviral Therapy, Highly Active
Trimethoprim-Sulfamethoxazole Combination
anemia
neutropenia
safety
hematologic toxicity

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Neutropenia
Agranulocytosis
Hematologic Diseases
Immune System Diseases
Lentivirus Infections
Leukocyte Disorders
Leukopenia
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Renal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014