Community Access to Rectal Artesunate for Malaria

NCT03568344 | Completed

• 1 other identifier: P 001-17-1.2
• Study Type: observational
• Target: 13,758
• Locations: 3 countries
• Sites: 3

Brief Summary

Many malaria deaths occur in places where people have poor access to preventive and curative health services. Prompt access to quality health services is critical in the case of severe childhood diseases, among which severe malaria is particularly frequent in endemic areas. In communities where parenteral treatment of severe malaria is not available, the World Health Organization (WHO) recommends administration of a single rectal dose of artesunate (RAS) to children less than 6 years, followed by immediate referral to an appropriate facility where the full package of care for severe malaria can be provided. Many African countries have already endorsed the use of pre-referral RAS. But treatment guidelines vary widely across these countries and often do not align with the WHO recommendation. With the impending availability of quality-assured rectal artesunate (QA RAS) and countries poised to scale-up this intervention, it is critical to investigate the safe and effective implementation of RAS as part of a continuum of care for severe malaria patients. To ensure that RAS is well targeted, it is equally urgent to learn more about frequency, treatment seeking and risk factors for severe malaria at community level. The CARAMAL project has two major components: the pilot implementation of QA RAS in selected areas of the Democratic Republic of the Congo (DRC), Nigeria and Uganda, and operational research on the introduction of QA RAS into established integrated community case management (iCCM) platforms. The CARAMAL project is funded by Unitaid and coordinated by the Clinton Health Access Initiative, Inc. (CHAI). UNICEF is responsible for QA RAS implementation. Swiss TPH in partnership with the local research organizations Akena Associates Ltd. in Nigeria, Kinshasa School of Public Health in DRC and Makerere University School of Public Health in Uganda carries out the operational research component to generate evidence for the responsible implementation of RAS. Finally, the CARAMAL project will generate a better understanding of severe febrile illness, its management at all levels and key determinants of health outcomes.

Conditions

Malaria

Keywords

Severe malaria; Mortality; Referral; Rectal artesunate; iCCM; Community based treatment

Outcome Measures

Primary Outcomes (1)

• Proportion of children <5 years with severe febrile illness seen by CHW/primary HF that resulted in death within 28 days

  Patient surveillance system (data collected at referral facility at 28 days visit including verbal autopsy)

  From RAS administration up to 28 days

Secondary Outcomes (16)

• Proportion of children <5 years with severe febrile illness without parasites on day 28

  28 days after RAS administration

• Proportion of children <5 years with a recent history of fever (mild or severe) who attend CHW/primary HF

  Through study completion, an average of 2 years

• Proportion of children <5 years with severe febrile illness seen by CHW/primary HF who completed referral

  From RAS administration up to 28 days

• Number of children <5 years with severe febrile illness who report directly to referral health facility

  Through study completion, an average of 2 years

• Proportion of children <5 years with severe febrile illness managed pre-referral according to guidelines

  Through study completion, an average of 2 years

Study Arms (4)

Community based tx seeking: baseline

Children \<5 years of age seeking care for a current/recent febrile illness episode at the level of community based care providers in the study areas, including CHWs and primary health facilities during baseline period (no QA RAS administration).

tx seeking @ referral facility: baseline

Children \<5 years of age seeking care for a severe febrile illness episode directly at the referral facility during baseline period (no QA RAS administration).

Community based tx seeking: Post RAS

Children \<5 years of age seeking care for a current/recent febrile illness episode at the level of community based care providers in the study areas, including CHWs and primary health facilities after QA RAS roll-out (after pre-referral QA RAS administration).

tx seeking @ referral facility: Post RAS

Children \<5 years of age seeking care for a severe febrile illness episode directly at the referral facility after QA RAS roll-out ( no QA RAS administration).

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The PSS will include all children \<5 years of age seeking care for a current/recent febrile illness episode at the level of community based care providers in the study areas, including CHWs and primary health facilities. In addition, all children \<5 years of age seeking care for a severe febrile illness episode directly at the referral facility will be enrolled to evaluate treatment seeking, diagnosis, treatment and disease outcome. These children will be excluded from the case fatality ratio analysis. During baseline, RAS is expected not to be available at community level in the study area, and the PSS will enroll primarily children not treated with pre-referral RAS, whereas after RAS roll-out, RAS is expected to be administered at the level of community based health care providers.

You may qualify if:

• Patient surveillance system:
• Children \< 5 years
• History of fever plus danger signs indicative of severe febrile illness / suspected severe malaria, according to local iCCM guidelines
• Child referred to higher level facility by CHW/primary health facility, or, child directly attending a referral facility.
• Signed full consent form from parent / guardian
• Health care provider interview:
• CHW or health worker at peripheral health facility enrolled in the iCCM referral system who treats children \< 5 years OR
• Health care provider at referral hospitals treating children \< 5 years OR
• Any other health care provider in project area treating children \< 5 years
• Signed consent form
• Household survey:
• Household head and parent / caregiver of children \< 5 years
• Signed consent form from parent / guardian

You may not qualify if:

• Patient surveillance system:
• Children ≥ 5 years
• Children with no permanent residence in project area
• Health care provider interview:
• Health workers not treating children \< 5 years
• Health workers outside project area
• Health workers who do not speak any of the local languages
• Health workers employed since \< 1 month
• Household survey:
• Parents / guardians with no children \< 5 years
• Parents / guardians with no permanent residence in project area
• Parents / guardians who do not speak any of the local languages

Sponsors & Collaborators

• Swiss Tropical & Public Health Institute: lead
• UNITAID: collaborator
• UNICEF: collaborator
• Kinshasa School of Public Health: collaborator
• Akena Associates Ltd.: collaborator
• Clinton Health Access Initiative Inc.: collaborator
• Makerere University: collaborator

Study Sites (3)

Kinshasa School of Public Health, University of Kinshasa

Kinshasa, Democratic Republic of the Congo

Location

Akena Associates Ltd.

Abuja, Nigeria

Location

Makerere University School of Public Health

Kampala, Uganda

Location

Related Publications (5)

• Gomes MF, Faiz MA, Gyapong JO, Warsame M, Agbenyega T, Babiker A, Baiden F, Yunus EB, Binka F, Clerk C, Folb P, Hassan R, Hossain MA, Kimbute O, Kitua A, Krishna S, Makasi C, Mensah N, Mrango Z, Olliaro P, Peto R, Peto TJ, Rahman MR, Ribeiro I, Samad R, White NJ; Study 13 Research Group. Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet. 2009 Feb 14;373(9663):557-66. doi: 10.1016/S0140-6736(08)61734-1. Epub 2008 Dec 6.

  PMID: 19059639 BACKGROUND

• Lengeler C, Burri C, Awor P, Athieno P, Kimera J, Tumukunde G, Angiro I, Tshefu A, Okitawutshu J, Kalenga JC, Omoluabi E, Akano B, Ayodeji K, Okon C, Yusuf O, Brunner NC, Delvento G, Lee T, Lambiris M, Visser T, Napier HG, Cohen JM, Buj V, Signorell A, Hetzel MW; CARAMAL Consortium. Community access to rectal artesunate for malaria (CARAMAL): A large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda. PLOS Glob Public Health. 2022 Sep 6;2(9):e0000464. doi: 10.1371/journal.pgph.0000464. eCollection 2022.

  PMID: 36962706 DERIVED

• Signorell A, Awor P, Okitawutshu J, Tshefu A, Omoluabi E, Hetzel MW, Athieno P, Kimera J, Tumukunde G, Angiro I, Kalenga JC, Akano BK, Ayodeji K, Okon C, Yusuf O, Delvento G, Lee TT, Brunner NC, Lambiris MJ, Okuma J, Cereghetti N, Buj V, Visser T, Napier HG, Lengeler C, Burri C. Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study. PLoS Med. 2023 Feb 21;20(2):e1004189. doi: 10.1371/journal.pmed.1004189. eCollection 2023 Feb.

  PMID: 36809247 DERIVED

• Hetzel MW, Okitawutshu J, Tshefu A, Omoluabi E, Awor P, Signorell A, Brunner NC, Kalenga JC, Akano BK, Ayodeji K, Okon C, Yusuf O, Athieno P, Kimera J, Tumukunde G, Angiro I, Delvento G, Lee TT, Lambiris MJ, Kwiatkowski M, Cereghetti N, Visser T, Napier HG, Cohen JM, Buj V, Burri C, Lengeler C. Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study. BMC Med. 2022 Oct 11;20(1):343. doi: 10.1186/s12916-022-02541-8.

  PMID: 36217159 DERIVED

• Brunner NC, Omoluabi E, Awor P, Okitawutshu J, Tshefu Kitoto A, Signorell A, Akano B, Ayodeji K, Okon C, Yusuf O, Athieno P, Kimera J, Tumukunde G, Angiro I, Kalenga JC, Delvento G, Lee TT, Lambiris MJ, Ross A, Cereghetti N, Visser T, Napier HG, Buj V, Burri C, Lengeler C, Hetzel MW. Prereferral rectal artesunate and referral completion among children with suspected severe malaria in the Democratic Republic of the Congo, Nigeria and Uganda. BMJ Glob Health. 2022 May;7(5):e008346. doi: 10.1136/bmjgh-2021-008346.

  PMID: 35580913 DERIVED

Related Links

• New Unitaid grants help protect women and children from malaria

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Christian Burri, Prof

  Swiss Tropical & Public Health Institute

  PRINCIPAL INVESTIGATOR

• Christian Lengeler, Prof

  Swiss Tropical & Public Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: June 26, 2018
• Study Start: June 15, 2018
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2021
• Last Updated: February 17, 2022

Record last verified: 2021-01

Locations

DE (1); NG (1); UG (1)