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Comparison of Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Adults

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ClinicalTrials.gov Identifier: NCT02218320
Recruitment Status : Completed
First Posted : August 18, 2014
Results First Posted : October 29, 2018
Last Update Posted : December 25, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Type Observational
Study Design Observational Model: Other;   Time Perspective: Prospective
Condition Human Immunodeficiency Virus
Interventions Drug: Raltegravir
Drug: Dolutegravir
Procedure: Colonoscopy with biopsy
Enrollment 20
Recruitment Details Recruitment began upon IRB approval. Patients were enrolled from December 2014 to October 2015, at which time data analysis ensued. Enrollment continued until 20 subjects completed all study procedures. Patients were recruited from the Infectious Disease clinics associated with the University of North Carolina at Chapel Hill.
Pre-assignment Details After informed consent, all patients underwent a screening visit to determine eligibility. This visit had to occur within the 6 weeks prior to study enrollment. Patients were enrolled into the group that matched their treatment regimen.
Arm/Group Title Group A Group B
Hide Arm/Group Description

Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Raltegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Dolutegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Period Title: Overall Study
Started 10 [1] 10 [2]
Completed 10 [3] 10 [4]
Not Completed 0 0
[1]
First participant visit on this arm Dec 2014
[2]
First participant contact on this arm was December 2014
[3]
Last participant contact on this arm was June 2015
[4]
Last participant contact on this arm was October 2015
Arm/Group Title Group A Group B Total
Hide Arm/Group Description

Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Raltegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.

Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Dolutegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.

Total of all reporting groups
Overall Number of Baseline Participants 10 10 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
10
 100.0%
20
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 20 participants
54.5
(48 to 64)
49.5
(32 to 56)
52.5
(32 to 64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Female
4
  40.0%
1
  10.0%
5
  25.0%
Male
6
  60.0%
9
  90.0%
15
  75.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
10
 100.0%
10
 100.0%
20
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
  70.0%
5
  50.0%
12
  60.0%
White
3
  30.0%
3
  30.0%
6
  30.0%
More than one race
0
   0.0%
2
  20.0%
2
  10.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 20 participants
10
 100.0%
10
 100.0%
20
 100.0%
1.Primary Outcome
Title Rectal Tissue Concentrations of Ralegravir and Dolutegravir
Hide Description [Not Specified]
Time Frame 2 to 6 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group A Group B
Hide Arm/Group Description:

Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Raltegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Dolutegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Overall Number of Participants Analyzed 10 10
Median (Full Range)
Unit of Measure: ng/g
5308
(3938 to 19600)
810
(510 to 1408)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group A, Group B
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title RNA Concentrations From Gastrointestinal Tissues
Hide Description We measured RNA concentrations in copies/1000cells for both drug groups
Time Frame 2 to 6 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group A Group B
Hide Arm/Group Description:

Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Raltegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Dolutegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Overall Number of Participants Analyzed 10 10
Median (Full Range)
Unit of Measure: copies/1000cells
0.05
(0.03 to 0.34)
0.16
(0.01 to 36.19)
3.Primary Outcome
Title Percentage of Total CD8+ T-cells With CCR5 Expression
Hide Description Local immunologic markers in gastrointestinal tract tissues
Time Frame 2 to 6 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group A Group B
Hide Arm/Group Description:

Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Raltegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Dolutegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Overall Number of Participants Analyzed 10 10
Median (Full Range)
Unit of Measure: percentage of total cells
0.15
(0.07 to 0.52)
0.64
(0.24 to 1.60)
Time Frame Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling).
Adverse Event Reporting Description Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.
 
Arm/Group Title Group A Group B
Hide Arm/Group Description

Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Raltegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.

Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.

Dolutegravir

Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples.

All-Cause Mortality
Group A Group B
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/10 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Group A Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group A Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/10 (30.00%)      3/10 (30.00%)    
Blood and lymphatic system disorders     
Thombophlebitis  [1]  0/10 (0.00%)  0 1/10 (10.00%)  1
Gastrointestinal disorders     
Anal Irritation  [2]  1/10 (10.00%)  1 0/10 (0.00%)  0
Abdominal gas cramps  [3]  1/10 (10.00%)  1 1/10 (10.00%)  1
Diarrhea  [4]  1/10 (10.00%)  1 0/10 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Hypertension  [5]  0/10 (0.00%)  0 1/10 (10.00%)  1
Indicates events were collected by systematic assessment
[1]
Onset 26Apr15, resolution 15May15, treated with Clindamycin
[2]
Onset and resolution 28Jan2015. Participant used aloe wipe on anus and symptoms resolved.
[3]
Onset and resolution 06Jan2015. Patient ambulated to resolution of symptoms with one dose of Tylenol.
[4]
Onset 13Dec14 and resolution 18Dec14. Resolved without treatment.
[5]
Elevated reading of blood pressure were noted on study, beginning 04May2015. Participant referred to PCP for management.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Angela Kashuba
Organization: University of North Carolina at Chapel Hill
Phone: 919 966-9998
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02218320     History of Changes
Other Study ID Numbers: 14-1647
First Submitted: August 13, 2014
First Posted: August 18, 2014
Results First Submitted: February 27, 2017
Results First Posted: October 29, 2018
Last Update Posted: December 25, 2018