OneRIF: Optimization of the TB Treatment Regimen Cascade

• Sponsor: Damien Foundation (Other)
• Overall Status: Completed
• CT.gov ID: NCT02153528
• Collaborator: National TB control Programme Bangladesh (Other), Institute of Tropical Medicine, Belgium (Other)
• Enrollment: 701
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 21.3

Study Details

Study Description

Brief Summary

• Hypothesis: Double dose rifampicin together with earlier monitoring of sputum conversion using vital staining reduces unfavorable outcome of Cat. 1 first-line TB treatment without excess serious toxicity, and allows early switch to specific treatment of MDR-TB without using Cat. 2 retreatment regimen

• General study design: This open label, randomised clinical trial is intended as a pilot study on the efficacy and safety of high-dose rifampicin and feasibility and added value of auramine and/or FDA vital staining sputum smear after 2 weeks of intensive treatment phase. If this proof-of-concept study provides substantial indication of benefit without indication of excess toxicity, the data from the study will be used to design a larger scale, cluster-randomized study. The aim of this cluster randomised study would be to provide definite proof of the benefit of the intervention on adverse treatment outcomes and lack of excess toxicity associated with high dose rifampicin. In addition, the cluster-randomized study would provide a more precise assessment of the suppression and prevention of (acquired) resistance endpoints.

An interim analysis is thus planned at the time the last recruited patient finishes treatment, i.e. about 9 months after the end of recruitment. It will focus on assessment of drug toxicity versus suggested benefits of the intervention. This analysis will be primarily performed for the go/no-go decision and design considerations for the cluster-randomized trial. The decision on proceeding to the cluster randomized study will be based on the absence of excess toxicity, a trend toward a reduction of unfavourable outcomes (excluding relapse), and possible favourable effects on initially present low-resistance mutations / mutations acquired during treatment. It will also allow to adapt the design of the larger study particularly regarding the algorithm for resistance screening, and whether or not treatment shortening could be justified with rapid initial conversion.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis, Pulmonary	Drug: double rimfampicin; Drug: Standard TB treatment	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 701 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optimization of the TB Treatment Regimen Cascade
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard TB treatment Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	Drug: Standard TB treatment; Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease; Other Names: Control arm
Experimental: double rimfampicin 2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout	Drug: double rimfampicin; Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained; Other Names: Intervention arm

Outcome Measures

Primary Outcome Measures

1. Tuberculose Treatment Outcome [12 months after end of treatment]

   Following current WHO guidelines, an adverse treatment outcome is defined as any occurrence of the following: Relapse: Cured previously from TB or completed treatment for TB and now having bacteriologically positive sputum for TB (at 12 months follow-up or at an earlier time point) Default: The patient whose treatment was interrupted for ≥ 2 consecutive months. Failure: Sputum positive for TB at 5 months or later during treatment. In line with current WHO recommendations, patients detected with MDR-TB or rifampicin resistance before this or another outcome applies and switched to the MDR-TB regimen will be excluded from the outcome analysis.18 Failure will also be declared if the regimen has to be changed for at least 2 drugs due to adverse events. Death: All-cause mortality between case registration and end of TB treatment (related or not to TB or TB treatment)

2. Number of Participants Who Develop Liver Toxicity [until month eight]

   Grade 3-4 Liver Toxicity following NIH common toxicity criteria (CTC), including transaminase increases to >5-20 ULN (grade 3), or > 20 ULN (grade 4)

Secondary Outcome Measures

1. High-level Rifampicin Resistant TB Adverse Treatment Outcomes [12 months after end of TB treatment]

   To assess whether the study regimen also cures high-level rifampicin resistant TB. Adverse treatment outcomes will be described and compared among treatment groups in subgroups defined by initial rifampicin resistance mutations (performed in all patients) detected.

2. Number of Initial Resistant TB Cases Who Switched to MDR-TB Treatment or Were Cured [at two weeks of treatment]

   To assess the effectiveness of FDA vital staining versus fever screening for early switch of non-responding rifampicin resistant TB to MDR-TB treatment

3. the Negative Predictive Value of Conversion at 2 Weeks for Relapse. [at 2 weeks of treatment]

   The Negative Predictive value (and 95% CI) of conversion in the intervention arm will be estimated as the % of relapses among those with a minimum 1 log decline in the number of AFB, or who are already negative or only scanty positive on AFB smear (auramine or FDA).

4. Proportion of Acquired Rifampicin Resistance Among Failures and Relapses [12 months after end of TB treatment]

   number of failure / relapse cases without mutation detected at diagnosis as the denominator and comparing intervention and control arms.

5. Area Under the Curve of Auramine Resp. FDA at 2 Weeks to Predict Adverse Treatment Outcome at 1 Year After Treatment Completion [Auramine/FDA at 2 weeks and adverse treatment outcome 1 year after treatment completion]

   Area under the ROC curve (AUC) to predict adverse treatment outcome. The X-axis represents the 1-specificity, the Y-axis represents sensitivity. The AUC is estimated with 95% confidence interval.

6. Weight Gain [until end of treatment (month eight)]

   Weight gain from baseline until end-of-treatment comparison between both treatment arms.

7. Fever Resolution [after 2 weeks of treatment]

   Comparison of fever resolution after 2 weeks of treatment between both treatment arms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with smear-positive pulmonary TB

• 15 years or older

• Able and willing to provide written informed consent

Exclusion Criteria:

• contacts of MDR-TB patients and other MDR-TB suspects diagnosed with resistance on rapid DST for rifampicin performed prior to start of treatment according to NTP guidelines

• smear-negative pulmonary and extra-pulmonary TB cases

• patients in need of hospitalization because of very bad general condition or complications

• patients with clinically active liver disease, for the study defined as jaundice confirmed by a local Medical Officer (Government)

• any known HIV-positive patient (although none are expected)

• any patient with known hepatitis B or C infection

• pregnant women; in addition, patients in the intervention arm who become pregnant during treatment will be switched to the control arm

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Damien Foundation Bangladesh TB project in Greater Mymensingh district (8 selected clinics)	Dhaka	Greater Mymensingh District	Bangladesh

Sponsors and Collaborators

• Damien Foundation
• National TB control Programme Bangladesh
• Institute of Tropical Medicine, Belgium

Investigators

• Principal Investigator: Aung Kya Jai Maug, MD, Damien Foundation Bangladesh

Study Documents (Full-Text)

• Study Protocol - Apr 15, 2015
• Statistical Analysis Plan - Sep 18, 2015

More Information

Publications

None provided.

• Responsible Party: Damien Foundation
• ClinicalTrials.gov Identifier: NCT02153528
• Other Study ID Numbers: OneRIF
• First Posted: Jun 3, 2014
• Last Update Posted: Feb 13, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Damien Foundation: Bangladesh; Rimfapicin
• Additional relevant MeSH terms: Tuberculosis; Tuberculosis, Pulmonary

Study Results

Participant Flow

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Period Title: Overall Study
STARTED	348	353
COMPLETED	348	353
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard TB Treatment	Double Rimfampicin	Total
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained	Total of all reporting groups
Overall Participants	346	352	698
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	42	45	44
Sex/Gender, Customized (Count of Participants)
Male	251 72.5%	260 73.9%	511 73.2%
Female	95 27.5%	92 26.1%	187 26.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Weight (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	41	42	41.5
Height (cm) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cm]	159	158	159
Temperature (°F) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [°F]	99.1	99.2	99.2
Direct smear auramine (Acid Fast Bacilli/field) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Acid Fast Bacilli/field]	98	90.0	93.3
Intervention smear auramine (AFB/field) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [AFB/field]	NA	100.0	100.0
Intervention smear FDA (number of AFB) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [number of AFB]	NA	10.0	10.0
ALT (IU/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [IU/L]	20	20	20
New case of TB (Count of Participants)
No	20 5.8%	29 8.2%	49 7%
Yes	326 94.2%	323 91.8%	649 93%
Diabetes (Count of Participants)
No	331 95.7%	335 95.2%	666 95.4%
Yes	15 4.3%	17 4.8%	32 4.6%
Liver problems (Count of Participants)
No	346 100%	351 99.7%	697 99.9%
Yes	0 0%	1 0.3%	1 0.1%
Kidney problems (Count of Participants)
No	346 100%	351 99.7%	697 99.9%
Yes	0 0%	1 0.3%	1 0.1%
Lung/Heart problems (Count of Participants)
No	344 99.4%	349 99.1%	693 99.3%
Yes	2 0.6%	3 0.9%	5 0.7%
Sign of Hepatitis (Count of Participants)
No	346 100%	352 100%	698 100%
Yes	0 0%	0 0%	0 0%
Cough (Count of Participants)
No	1 0.3%	1 0.3%	2 0.3%
Yes	345 99.7%	351 99.7%	696 99.7%

Outcome Measures

1. Primary Outcome

Title	Tuberculose Treatment Outcome
Description	Following current WHO guidelines, an adverse treatment outcome is defined as any occurrence of the following: Relapse: Cured previously from TB or completed treatment for TB and now having bacteriologically positive sputum for TB (at 12 months follow-up or at an earlier time point) Default: The patient whose treatment was interrupted for ≥ 2 consecutive months. Failure: Sputum positive for TB at 5 months or later during treatment. In line with current WHO recommendations, patients detected with MDR-TB or rifampicin resistance before this or another outcome applies and switched to the MDR-TB regimen will be excluded from the outcome analysis.18 Failure will also be declared if the regimen has to be changed for at least 2 drugs due to adverse events. Death: All-cause mortality between case registration and end of TB treatment (related or not to TB or TB treatment)
Time Frame	12 months after end of treatment

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis. Additional 4 subjects were removed from the ITT analysis because they switched to MDR regimen (3 in control arm, 1 in intervention arm). 4 subjects (intervention arm) were removed from the ITT analysis because they were enrolled twice.

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Measure Participants	343	347
Default	8 2.3%	8 2.3%
Died	11 3.2%	5 1.4%
Failure	8 2.3%	12 3.4%
Completed	6 1.7%	3 0.9%
Cured	310 89.6%	319 90.6%

2. Primary Outcome

Title	Number of Participants Who Develop Liver Toxicity
Description	Grade 3-4 Liver Toxicity following NIH common toxicity criteria (CTC), including transaminase increases to >5-20 ULN (grade 3), or > 20 ULN (grade 4)
Time Frame	until month eight

Outcome Measure Data

Analysis Population Description

One participant was allocated to double rifampicin arm but received standard TB treatment, and was analysed in the standard TB treatment arm.Two participants were deleted from analysis because they had grade 3 liver toxicity at baseline and 6 participants were deleted because they did not have any follow-up ALT values.

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Measure Participants	343	350
Count of Participants [Participants]	7 2%	3 0.9%

3. Secondary Outcome

Title	High-level Rifampicin Resistant TB Adverse Treatment Outcomes
Description	To assess whether the study regimen also cures high-level rifampicin resistant TB. Adverse treatment outcomes will be described and compared among treatment groups in subgroups defined by initial rifampicin resistance mutations (performed in all patients) detected.
Time Frame	12 months after end of TB treatment

Outcome Measure Data

Analysis Population Description

ITT analysis population. Compared to analysis population of primary objective - TB treatment outcome, 24 subjects were excluded from this analysis due to missing or negative sequencing results (8 in control group, 16 in intervention group).

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Measure Participants	335	331
Rif-sensitive with adverse treatment outcome	52 15%	40 11.4%
Rif-sensitive cured/completed without relapse	281 81.2%	290 82.4%
Rif-resistant with adverse treatment outcome	0 0%	0 0%
Rif-resistant cured/completed without relapse	2 0.6%	1 0.3%

4. Secondary Outcome

Title	Number of Initial Resistant TB Cases Who Switched to MDR-TB Treatment or Were Cured
Description	To assess the effectiveness of FDA vital staining versus fever screening for early switch of non-responding rifampicin resistant TB to MDR-TB treatment
Time Frame	at two weeks of treatment

Outcome Measure Data

Analysis Population Description

7 initial resistant cases (5 in control group and 2 in intervention group).

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Measure Participants	5	2
Count of Participants [Participants]	5 1.4%	2 0.6%

5. Secondary Outcome

Title	the Negative Predictive Value of Conversion at 2 Weeks for Relapse.
Description	The Negative Predictive value (and 95% CI) of conversion in the intervention arm will be estimated as the % of relapses among those with a minimum 1 log decline in the number of AFB, or who are already negative or only scanty positive on AFB smear (auramine or FDA).
Time Frame	at 2 weeks of treatment

Outcome Measure Data

Analysis Population Description

ITT analysis. This analysis only includes participants in the intervention arm who are negative on auramine smear resp. FDA smear at 2 weeks.

Arm/Group Title	Double Rifampicin Arm Negative on Auramine Smear	Double Rifampicin Group Negative on FDA Smear
Arm/Group Description	This outcome is only calculated for the intervention arm.	This outcome is only analysed for the intervention arm.
Measure Participants	91	193
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Proportion of Acquired Rifampicin Resistance Among Failures and Relapses
Description	number of failure / relapse cases without mutation detected at diagnosis as the denominator and comparing intervention and control arms.
Time Frame	12 months after end of TB treatment

Outcome Measure Data

Analysis Population Description

ITT analysis. This analysis only includes failure / relapse cases without mutation detected at diagnosis

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Measure Participants	8	12
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Area Under the Curve of Auramine Resp. FDA at 2 Weeks to Predict Adverse Treatment Outcome at 1 Year After Treatment Completion
Description	Area under the ROC curve (AUC) to predict adverse treatment outcome. The X-axis represents the 1-specificity, the Y-axis represents sensitivity. The AUC is estimated with 95% confidence interval.
Time Frame	Auramine/FDA at 2 weeks and adverse treatment outcome 1 year after treatment completion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Double Rifampicin Arm Negative on Auramine Smear	Double Rifampicin Group Negative on FDA Smear
Arm/Group Description	This outcome is only calculated for the intervention arm.	This outcome is only analysed for the intervention arm.
Measure Participants	344	344
Number (95% Confidence Interval) [no unit is used for AUROC]	0.52	0.54

8. Secondary Outcome

Title	Weight Gain
Description	Weight gain from baseline until end-of-treatment comparison between both treatment arms.
Time Frame	until end of treatment (month eight)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Measure Participants	320	331
Mean (Standard Deviation) [kg]	2.93 (2.44)	2.79 (2.44)

9. Secondary Outcome

Title	Fever Resolution
Description	Comparison of fever resolution after 2 weeks of treatment between both treatment arms.
Time Frame	after 2 weeks of treatment

Outcome Measure Data

Analysis Population Description

Total of participants with fever at baseline.

Arm/Group Title	Standard TB Treatment	Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease	2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
Measure Participants	82	72
Count of Participants [Participants]	81 23.4%	71 20.2%

Adverse Events

Time Frame	Serious adverse events are recorded until end of treatment (up to 8 months). No (non-serious) adverse events are recorded in this trial.
Arm/Group Title	Standard TB Treatment		Double Rimfampicin
Arm/Group Description	Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease Standard TB treatment: Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease		2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout double rimfampicin: Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained
All Cause Mortality
	Standard TB Treatment		Double Rimfampicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/348 (4.9%)		12/353 (3.4%)
Serious Adverse Events
	Standard TB Treatment		Double Rimfampicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/348 (6.9%)		13/353 (3.7%)
Cardiac disorders
Cardiopulmonary failure	1/348 (0.3%)		1/353 (0.3%)
Gastrointestinal disorders
Abdominal pain	1/348 (0.3%)		0/353 (0%)
Vomiting	2/348 (0.6%)		0/353 (0%)
General disorders
Asthenia	0/348 (0%)		1/353 (0.3%)
Hepatobiliary disorders
Hepatitis	2/348 (0.6%)		1/353 (0.3%)
Jaundice	4/348 (1.1%)		5/353 (1.4%)
Investigations
Alanine aminotransferase increased	5/348 (1.4%)		2/353 (0.6%)
Metabolism and nutrition disorders
Decreased appetite	1/348 (0.3%)		1/353 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/348 (0%)		1/353 (0.3%)
Gallbladder cancer metastatic	0/348 (0%)		1/353 (0.3%)
Malignant neoplasm	1/348 (0.3%)		0/353 (0%)
Nervous system disorders
Ataxia	1/348 (0.3%)		0/353 (0%)
Cerebrovascular accident	1/348 (0.3%)		1/353 (0.3%)
Ischaemic stroke	0/348 (0%)		1/353 (0.3%)
Renal and urinary disorders
Anuria	1/348 (0.3%)		0/353 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	2/348 (0.6%)		0/353 (0%)
Pleural effusion	1/348 (0.3%)		0/353 (0%)
Respiratory distress	2/348 (0.6%)		0/353 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/348 (0%)		1/353 (0.3%)
Social circumstances
Victim of homicide	1/348 (0.3%)		0/353 (0%)
Other (Not Including Serious) Adverse Events
	Standard TB Treatment		Double Rimfampicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/348 (0%)		0/353 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.