Paradoxical Tuberculosis Reactions in Patients Without HIV Infection

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 8, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a surprising reaction some people with tuberculosis (TB) have during treatment, known as a paradoxical reaction. While most people start to feel better after beginning treatment, some may initially improve but then suddenly feel worse. Researchers aim to understand why this happens and what it means for patients.

To participate, you must be an adult aged 18 or older who has been diagnosed with TB and has been on treatment for at least two weeks. You should also have experienced certain signs that suggest a paradoxical reaction, like worsening symptoms or changes in test results after feeling better. If eligible, you would visit the NIH Clinical Center three times over six to 18 months. Each visit will involve a physical exam, blood and urine tests, as well as special scans that take pictures of your body. This study is important for helping doctors understand how to better treat TB and support patients who experience these unexpected reactions.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• Suspected Paradoxical Reaction Group Criteria:
• • 1. Aged greater than or equal to 18 years.
• 2. Diagnosed with confirmed (microbiologically or with molecular methods) or suspected (clinical plus or minus histologic diagnosis) TB and currently on ATT for a minimum of 2 weeks, or have completed ATT, with at least 2 of the following signs/symptoms of a paradoxical inflammatory reaction:
• • Recrudescent symptoms of TB after initial clinical improvement.
• • Change in physical exam after initial clinical improvement suggestive of new inflammatory process (e.g., lymphadenopathy or new findings on pulmonary exam).
• • Worsening radiographic evidence of disease after initiation of treatment, as compared with imaging prior to or earlier in treatment.
• • Laboratory evidence of acute inflammatory response, including the development of leukocytosis (white blood cell count \> 10,000 cells/microL) or a change of C-reactive protein (CRP) \> 5 mg/L compared to prior laboratory values.
• • Worsened organ function after initial clinical improvement.
• • 3. The above sign/symptom(s) cannot be explained by a newly acquired infection, clinical course of a previously recognized infectious agent, side effects of the ATT, the presence of drug resistance, or any other condition except for paradoxical reaction.
• • 4. Willingness to allow storage of blood or tissue samples for future research.
• • 5. Ability of participant to understand study requirements and give informed consent.
• • 6. Has a primary care physician and is being followed by the local Department of Health for their TB (or has plans to arrange after enrollment if enrolled early in course from inpatient transfer).
• Control Group Criteria:
• • 1. Aged greater than or equal to 18 years.
• • 2. Diagnosed with confirmed (microbiologically or with molecular methods) or suspected (clinical plus or minus histologic diagnosis) TB.
• • 3. Presenting 2 to 4 months after starting ATT to match timing of paradoxical reactions.
• • 4. Willingness to allow storage of blood or tissue samples for future research.
• • 5. Ability of participant to understand study requirements and give informed consent.
• • 6. Has a primary care physician and is being followed by the Department of Health for their TB (or has plans to arrange after enrollment if enrolled early in course from inpatient transfer).
• EXCLUSION CRITERIA:
• Individuals in either group who meet any of the following criteria will be excluded from study participation:
• • 1. HIV infection. (Individuals with HIV infection may be eligible for a separate study exclusively evaluating persons living with HIV.)
• • 2. Pregnant or breastfeeding.
• • 3. Uncontrolled psychiatric disease, substance use, or inappropriate conduct unsuitable for a research study.
• • 4. Malignancy requiring imminent or ongoing treatment including radiation, chemotherapy, or immunotherapy.
• • 5. Debilitating or chronic conditions that would limit ability to participate in the study.
• • 6. Emergent or urgent clinical conditions not due to studied disease of interest requiring immediate treatment that would be unsuitable for a research study. These patients would be transferred to an emergency room and able to rescreen when condition has been stabilized.